USMLE Step 1 Practice Questions: 25 Free Examples with Explanations

If you’re looking for USMLE Step 1 sample questions that feel like the real deal (and teach you something), you’re in the right place. Step 1 rewards pattern recognition, test-taking strategy, and rock-solid fundamentals—and the fastest way to build all three is by drilling high-quality questions with clear explanations.

Below are 25 of our USMLE Step 1 practice questions pulled from the MedBoardTutors question bank, organized by difficulty (Easy, Medium, Hard). Each one includes an Answer & Explanation section right after the stem so you can learn efficiently, fix your weak points, and move on.

Easy Questions (1–10)

Below are 25 of our USMLE Step 1 practice questions pulled from the MedBoardTutors question bank, organized by difficulty (Easy, Medium, Hard). Each one includes an Answer & Explanation section right after the stem so you can learn efficiently, fix your weak points, and move on.

Question 1 — Young woman with fatigue, pallor, and heavy menses

Heme

A 24-year-old woman comes to the clinic secondary to a 3-month history of fatigue and pallor. She has heavy menstrual bleeding during her periods. She follows a vegetarian diet but admits to irregular eating habits. Physical examination shows pale conjunctivae and a soft systolic murmur.

Laboratory studies reveal:
Hemoglobin: 8.1 g/dL
Mean corpuscular volume (MCV): 70 fL
Serum ferritin: Low
Total iron-binding capacity (TIBC): Elevated

Which of the following is the most likely cause of her anemia?

1. Anemia of chronic disease
2. Folate deficiency
3. Iron deficiency anemia
4. Thalassemia minor
5. Vitamin B12 deficiency

Answer: C) Iron deficiency anemia

Why this is correct

This patient presents with microcytic anemia, low ferritin, elevated TIBC, and history of heavy menses are consistent with iron deficiency anemia, the most common cause in young women with menstrual blood loss.

Why the others are wrong

• A) Anemia of chronic disease typically presents with normal or high ferritin and low TIBC.
• B) Folate deficiency causes macrocytic anemia, not microcytic.
• D) Thalassemia minor causes microcytosis but usually with normal iron studies.
• E) B12 deficiency causes macrocytosis, not microcytosis.

Educational Objective

Iron deficiency anemia is caused by insufficient iron, commonly secondary to chronic blood loss in menstruating women.

Tutor Insight

Remember: Low ferritin, small cells, heavy periods.

Question 2 — Calf swelling after long flight

Vascular

A 28-year-old woman presents with left calf pain and swelling for the past 2 days. She recently returned from a 12-hour international flight. Examination reveals swelling, warmth, and tenderness of the left calf. Dorsiflexion of the foot elicits pain. Doppler ultrasonography reveals a noncompressible left popliteal vein.

Which of the following is the most appropriate initial treatment?

1. Intravenous alteplase
2. Oral aspirin therapy
3. Oral warfarin initiation without bridging
4. Subcutaneous low-molecular-weight heparin
5. Thrombectomy

Answer: D) Subcutaneous low-molecular-weight heparin

Why this is correct

This patient presents with classic signs of deep vein thrombosis (DVT) after prolonged immobilization are best treated initially with low-molecular-weight heparin unless contraindications exist.

Why the others are wrong

• A) Alteplase is used for massive pulmonary embolism with hemodynamic instability, not isolated DVT.
• B) Aspirin is insufficient to treat DVT.
• C) Warfarin requires bridging with a faster-acting anticoagulant initially.
• E) Thrombectomy is reserved for limb-threatening DVT (phlegmasia cerulea dolens).

Educational Objective

First-line treatment of DVT is anticoagulation with low-molecular-weight heparin.

Tutor Insight

Remember: Swollen flight calf.

Question 3 — Vaginal discharge with clue cells

Gyn

A 34-year-old woman presents to the clinic secondary to vaginal irritation and a malodorous discharge. She reports that the discharge is thin, gray-white, and worsens after intercourse. She is sexually active with multiple partners and inconsistently uses condoms. On examination, there is no cervical motion tenderness or adnexal mass. Wet mount microscopy shows clue cells.

Which of the following is the most appropriate treatment?

1. Ceftriaxone intramuscular injection
2. Doxycycline oral therapy
3. Fluconazole oral therapy
4. Metronidazole oral therapy
5. Penicillin G intramuscular injection

Answer: D) Metronidazole oral therapy

Why this is correct

This patient presents with thin, gray, malodorous discharge and clue cells are diagnostic of bacterial vaginosis, which is treated with oral metronidazole.

Why the others are wrong

• A) Ceftriaxone is used for gonorrhea, not BV.
• B) Doxycycline treats chlamydia but not BV.
• C) Fluconazole treats candidiasis, which typically presents with thick, white discharge.
• E) Penicillin G is used for syphilis.

Educational Objective

Bacterial vaginosis presents with thin, malodorous discharge and is treated with oral metronidazole.

Tutor Insight

Remember: Fishy smell plus clue cells.

Question 4 — Burning urination with positive leukocyte esterase

Renal

A 22-year-old woman presents with burning sensation during urination and increased urinary frequency for 2 days. She denies fever, flank pain, or vaginal discharge. She is sexually active with one partner. On examination, her abdomen is soft without costovertebral angle tenderness. Urinalysis shows positive leukocyte esterase, positive nitrites, and numerous white blood cells.

Which of the following is the most appropriate next step in management?

1. Intravenous ceftriaxone
2. Oral azithromycin
3. Oral cefalexin
4. Oral metronidazole
5. Oral vancomycin

Answer: C) Oral cefalexin

Why this is correct

This patient's dysuria, frequency, positive leukocyte esterase and nitrites is consistent with uncomplicated cystitis, and she should be treated with an oral antibiotic such as cefalexin (or nitrofurantoin, or TMP-SMX).

Why the others are wrong

• A) IV antibiotics are reserved for pyelonephritis or complicated infections.
• B) Azithromycin treats chlamydial urethritis, not E. coli cystitis.
• D) Metronidazole is for anaerobic infections, not urinary tract infections.
• E) Oral vancomycin treats C. difficile infection, not cystitis.

Educational Objective

Uncomplicated cystitis is treated with oral antibiotics targeting urinary tract pathogens.

Tutor Insight

Remember: Pee burns and no flank pain.

Question 5 — Positive pregnancy test with empty uterus

OB

A 29-year-old woman presents with a 1-week history of lower abdominal cramping and vaginal bleeding. Her last menstrual period was 6 weeks ago. She has mild suprapubic tenderness but no cervical motion tenderness or adnexal masses. Serum β-hCG is positive at a level consistent with 6 weeks' gestation. Transvaginal ultrasound shows an empty uterus.

Which of the following is the most likely explanation for these findings?

1. Complete molar pregnancy
2. Ectopic pregnancy
3. Missed abortion
4. Normal early intrauterine pregnancy
5. Threatened abortion

Answer: B) Ectopic pregnancy

Why this is correct

This patient presents with positive pregnancy test, empty uterus on ultrasound, vaginal bleeding, and mild abdominal pain are highly suggestive of ectopic pregnancy.

Why the others are wrong

• A) Complete mole would present with much higher β-hCG and a "snowstorm" appearance on ultrasound.
• C) Missed abortion would typically show an intrauterine gestational sac without fetal cardiac activity.
• D) By 6 weeks, an intrauterine pregnancy should be visible on transvaginal ultrasound.
• E) Threatened abortion shows an intrauterine pregnancy with fetal cardiac activity.

Educational Objective

Ectopic pregnancy must be suspected with positive β-hCG and no intrauterine pregnancy on ultrasound.

Tutor Insight

Remember: Pregnant but empty uterus.

Question 6 — Sinus pressure and purulent discharge >10 days

ENT/Infect

A 23-year-old woman comes to the clinic secondary to persistent nasal congestion and facial pressure. She reports thick nasal discharge and pain over her maxillary sinuses that worsens when leaning forward. These symptoms have been present for over 10 days without improvement. She denies any recent antibiotic use.

Which of the following is the most likely diagnosis?

1. Acute allergic rhinitis
2. Acute bacterial sinusitis
3. Acute viral upper respiratory infection
4. Chronic sinusitis
5. Deviated nasal septum

Answer: B) Acute bacterial sinusitis

Why this is correct

This patient presents with >10 days of purulent nasal discharge, sinus pressure, and lack of improvement are typical for acute bacterial sinusitis.

Why the others are wrong

• A) Allergic rhinitis causes clear discharge and sneezing.
• C) Viral URIs typically resolve within 7–10 days.
• D) Chronic sinusitis lasts >12 weeks.
• E) Deviated septum can cause congestion but not purulent discharge.

Educational Objective

Acute bacterial sinusitis is diagnosed when symptoms persist >10 days without improvement or worsen after initial recovery.

Tutor Insight

Remember: Face hurts past 10 days with pus.

Question 7 — Monoarthritis after urethritis

Infect/MSK

A 19-year-old man presents to the clinic with a painful, swollen right knee that started 2 days ago. He also reports urethral discharge that began one week ago but resolved spontaneously. He denies recent trauma. Examination shows a warm, swollen right knee with limited range of motion. No skin rash is noted. Synovial fluid analysis shows WBC count of 25,000/mm³, predominantly neutrophils, but no crystals are seen. Gram stain is negative.

Which of the following is the most likely diagnosis?

1. Crystal-induced arthritis
2. Gonococcal septic arthritis
3. Osteoarthritis
4. Rheumatoid arthritis
5. Viral arthritis

Answer: B) Gonococcal septic arthritis

Why this is correct

This young sexually active man with monoarthritis following urethritis, sterile synovial fluid Gram stain, and high WBC count strongly suggests disseminated gonococcal infection causing septic arthritis.

Why the others are wrong

• A) Crystal arthritis would show crystals on microscopy.
• C) Osteoarthritis causes chronic, noninflammatory joint pain.
• D) Rheumatoid arthritis typically presents with symmetric small joint involvement.
• E) Viral arthritis usually causes polyarthritis and mild symptoms.

Educational Objective

Gonococcal septic arthritis presents with monoarthritis or oligoarthritis, often with a negative Gram stain.

Tutor Insight

Remember: Sex, swelling, and sterile fluid.

Question 8 — Polydipsia/polyuria with response to desmopressin

Endocrine

A 38-year-old woman presents to the clinic secondary to increasing thirst and frequent urination. She drinks over 5 liters of water daily. Past medical history is unremarkable. Physical examination is normal.

Laboratory studies reveal:
Serum sodium: 148 mEq/L (high)
Serum osmolality: 310 mOsm/kg (high)
Urine osmolality: 100 mOsm/kg (low)
After administration of desmopressin, her urine osmolality increases to 500 mOsm/kg.

Which of the following is the most likely diagnosis?

1. Central diabetes insipidus
2. Nephrogenic diabetes insipidus
3. Primary polydipsia
4. Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
5. Uncontrolled diabetes mellitus

Answer: A) Central diabetes insipidus

Why this is correct

This patient presents with hypernatremia, dilute urine, and strong response to desmopressin are consistent with central diabetes insipidus, secondary to deficient ADH production.

Why the others are wrong

• B) Nephrogenic DI shows poor response to desmopressin.
• C) Primary polydipsia typically causes hyponatremia.
• D) SIADH causes low sodium and inappropriately concentrated urine.
• E) Diabetes mellitus would cause osmotic diuresis with glucosuria.

Educational Objective

Central diabetes insipidus is caused by ADH deficiency, corrected by desmopressin.

Tutor Insight

Remember: Dry, dilute, and desmo-responsive.

Question 9 — Post-op pleuritic chest pain with pleural effusion

Pulm/Vascular

A 45-year-old woman comes to the emergency department secondary to sharp right-sided chest pain that worsens with inspiration. She also reports mild shortness of breath but denies fever, cough, or hemoptysis. She recently underwent an open cholecystectomy 5 days ago and has been mostly bedridden at home. Her heart rate is 110/min and respiratory rate is 24/min. Oxygen saturation is 94% on room air. Lung examination reveals decreased breath sounds at the right base. Chest X-ray shows a small right-sided pleural effusion.

Which of the following is the most likely cause of this patient's current symptoms?

1. Atelectasis
2. Bacterial pneumonia
3. Pleural effusion secondary to pulmonary embolism
4. Postoperative diaphragmatic injury
5. Right-sided pneumothorax

Answer: C) Pleural effusion secondary to pulmonary embolism

Why this is correct

This patient presents with recent surgery, prolonged immobility, pleuritic chest pain, tachycardia, and small pleural effusion raise strong suspicion for pulmonary embolism (PE) complicated by pleural inflammation and effusion.

Why the others are wrong

• A) Atelectasis causes hypoxemia without pleuritic pain or effusion.
• B) Bacterial pneumonia typically presents with fever, productive cough, and consolidation on imaging.
• D) Diaphragmatic injury would usually follow trauma, not surgery like cholecystectomy.
• E) Pneumothorax presents with absent breath sounds and hyperresonance, not effusion.

Educational Objective

Pulmonary embolism can cause pleuritic chest pain and small pleural effusions secondary to infarction and inflammation.

Tutor Insight

Remember: Post-op chest pain with fluid.

Question 10 — Sore throat with splenomegaly and atypical lymphocytes

Infect

A 25-year-old man presents with sore throat, fever, and malaise for the past week. He also reports fatigue and decreased appetite. On examination, he has cervical lymphadenopathy, tonsillar exudates, and splenomegaly. A rapid streptococcal antigen test is negative. Heterophile antibody test is positive. Peripheral blood smear shows large, atypical lymphocytes.

Which of the following is the most likely causative agent?

1. Cytomegalovirus
2. Epstein-Barr virus
3. Group A Streptococcus
4. Human immunodeficiency virus
5. Toxoplasma gondii

Answer: B) Epstein-Barr virus

Why this is correct

This patient's fever, pharyngitis, lymphadenopathy, splenomegaly, positive heterophile (Monospot) test, and atypical lymphocytes are diagnostic of infectious mononucleosis caused by Epstein-Barr virus (EBV).

Why the others are wrong

• A) CMV can mimic mono but is heterophile-negative.
• C) Group A Strep causes pharyngitis but not splenomegaly or atypical lymphocytes.
• D) HIV can mimic mono early but usually has additional systemic findings.
• E) Toxoplasmosis primarily presents with isolated lymphadenopathy without tonsillitis.

Educational Objective

Infectious mononucleosis is caused by Epstein-Barr virus, presenting with fever, pharyngitis, and lymphadenopathy.

Tutor Insight

Remember: Big spleen plus sore throat.

Medium Questions (11–20)

Medium questions often add one more layer: a key association, a “next step” nuance, or a mechanism that forces you to think. These usmle step 1 sample questions are great for sharpening your differential and your underlying pathophysiology.

Question 11 — Recurrent infections with dextrocardia and absent thymus

Immuno

A 19-year-old man presents with recurrent respiratory infections and failure to thrive. Examination shows dextrocardia. Laboratory studies reveal absent B cells and low immunoglobulin levels. Imaging shows absence of a thymic shadow on chest x-ray.

Which of the following is the most likely underlying defect?

1. Defective expression of MHC class II molecules
2. Failure of development of the third and fourth pharyngeal pouches
3. Mutation in Bruton's tyrosine kinase gene
4. NADPH oxidase deficiency
5. T-cell receptor gene rearrangement failure

Answer: B) Failure of development of the third and fourth pharyngeal pouches

Why this is correct

Recurrent infections, thymic absence, and dextrocardia suggest DiGeorge syndrome (22q11.2 deletion). DiGeorge syndrome arises from failed development of the third and fourth pharyngeal pouches, leading to absent thymus and parathyroids. Dextrocardia and conotruncal cardiac anomalies are also common.

Why the others are wrong

• A) MHC II defects cause bare lymphocyte syndrome, leading to combined immunodeficiency but not heart defects.
• C) Bruton tyrosine kinase mutations cause X-linked agammaglobulinemia (B-cell deficiency without thymic hypoplasia).
• D) NADPH oxidase deficiency causes chronic granulomatous disease, leading to impaired neutrophil function.
• E) TCR rearrangement failure causes SCID but with both B and T cell issues and no specific cardiac defects.

Educational Objective

DiGeorge syndrome is caused by failure of third and fourth pharyngeal pouch development, leading to thymic hypoplasia, hypocalcemia, and cardiac anomalies.

Tutor Insight

No thymus plus cardiac issues = 22q11 deletion — not Bruton or bare lymphocyte syndrome where thymus is intact.

Question 12 — Fatigue and pruritus with bile duct strictures and UC history

GI/Hepato

A 63-year-old man presents with worsening fatigue and pruritus.

Laboratory studies reveal:
Alkaline phosphatase: Elevated
Total bilirubin: Elevated
Antimitochondrial antibodies: Negative
Magnetic resonance cholangiopancreatography (MRCP): Multifocal strictures and dilations of intrahepatic and extrahepatic bile ducts

He also has a history of ulcerative colitis.

Which of the following is the most likely diagnosis?

1. Autoimmune hepatitis
2. Cholangiocarcinoma
3. Primary biliary cholangitis
4. Primary sclerosing cholangitis
5. Secondary biliary cirrhosis

Answer: D) Primary sclerosing cholangitis

Why this is correct

Cholestatic liver enzyme pattern (high alk phos) with strictures/dilations on MRCP and a history of ulcerative colitis points toward primary sclerosing cholangitis (PSC). PSC is associated with progressive fibrosis of intra- and extrahepatic bile ducts and is closely linked to IBD.

Why the others are wrong

• A) Autoimmune hepatitis primarily elevates transaminases, not alk phos, and features positive anti-smooth muscle antibodies.
• B) Cholangiocarcinoma is a complication of PSC, not the initial diagnosis.
• C) PBC is limited to intrahepatic ducts and typically shows positive antimitochondrial antibodies.
• E) Secondary biliary cirrhosis is caused by known obstruction, not autoimmune fibrosis.

Educational Objective

Primary sclerosing cholangitis is a fibrosing inflammatory disease of bile ducts, highly associated with ulcerative colitis.

Tutor Insight

If you see a guy with IBD and bile duct strictures on imaging, it's PSC — not PBC, which favors middle-aged women and AMA positivity.

Question 13 — Episodic hypertension with adrenal mass

Endocrine

A 30-year-old woman presents with episodic palpitations, sweating, and headaches. She has hypertension that is difficult to control. Physical exam reveals a firm mass in the right flank. Laboratory studies reveal elevated urinary metanephrines and normetanephrines. Imaging identifies a right adrenal mass.

Which of the following embryologic derivatives is responsible for the cell type of the tumor?

1. Endoderm
2. Mesoderm
3. Neural crest
4. Surface ectoderm
5. Intermediate mesoderm

Answer: C) Neural crest

Why this is correct

Palpitations, episodic hypertension, and elevated metanephrines suggest pheochromocytoma. Pheochromocytomas arise from chromaffin cells of the adrenal medulla. Chromaffin cells originate from the neural crest.

Why the others are wrong

• A) Endoderm gives rise to the gut lining and associated organs, not adrenal medulla.
• B) Mesoderm forms muscle, bone, blood vessels, but not chromaffin cells.
• D) Surface ectoderm gives rise to skin and sensory epithelium, not adrenal tissue.
• E) Intermediate mesoderm contributes to the urinary and reproductive systems.

Educational Objective

Pheochromocytomas arise from neural crest–derived chromaffin cells that produce catecholamines.

Tutor Insight

Think neural crest for anything involving adrenal medulla, peripheral neurons, or melanocytes — not mesodermal derivatives like kidneys.

Question 14 — Sudden-onset left face and arm weakness with internal capsule infarct

Neuro

A 68-year-old man presents with sudden-onset weakness of the left face and arm. He has a history of hypertension, diabetes, and hyperlipidemia. On examination, he has a left-sided facial droop sparing the forehead, left arm weakness, and no sensory deficits. Brain CT reveals an infarct in the right internal capsule.

Which of the following best explains the pathogenesis of his stroke?

1. Atherosclerotic plaque rupture and thrombus formation
2. Cardioembolic event
3. Lipohyalinosis of small penetrating arteries
4. Rupture of a cerebral aneurysm
5. Vasculitis of cerebral vessels

Answer: C) Lipohyalinosis of small penetrating arteries

Why this is correct

Pure motor stroke affecting face and arm with internal capsule infarct suggests lacunar stroke. Lacunar strokes are caused by lipohyalinosis and microatheroma formation in small penetrating arteries secondary to chronic hypertension and diabetes. These strokes often spare sensory and cortical functions.

Why the others are wrong

• A) Large atherosclerotic plaque rupture usually causes cortical strokes.
• B) Cardioembolic events cause cortical strokes with multiple territory involvement.
• D) Cerebral aneurysm rupture causes subarachnoid hemorrhage, not ischemic infarct.
• E) Vasculitis affects multiple vascular territories and often presents with systemic features.

Educational Objective

Lacunar infarcts result from lipohyalinosis of small penetrating arteries, particularly in the setting of chronic hypertension and diabetes.

Tutor Insight

Pure motor stroke = small vessel disease (lipohyalinosis) — not large vessel plaque rupture or embolism.

Question 15 — Painless jaundice with bile duct dilation and no stones

GI/Onc

A 55-year-old man presents with jaundice, dark urine, and pale stools.

Laboratory studies reveal:
Alkaline phosphatase: Markedly elevated
AST and ALT: Mildly elevated
Total bilirubin: Elevated
Direct bilirubin: Elevated
Abdominal ultrasound: Intrahepatic and extrahepatic bile duct dilation but no stones

Which of the following is the most likely underlying cause?

1. Autoimmune hepatitis
2. Cholangiocarcinoma
3. Primary biliary cholangitis
4. Primary sclerosing cholangitis
5. Viral hepatitis

Answer: B) Cholangiocarcinoma

Why this is correct

Painless jaundice, dark urine, pale stools, and bile duct dilation without stones suggest biliary obstruction by a mass. Cholangiocarcinoma, a malignancy of bile duct epithelium, is a classic cause. Elevated direct bilirubin and marked alk phos elevation are consistent with cholestasis.

Why the others are wrong

• A) Autoimmune hepatitis causes primarily hepatocellular injury, not bile duct obstruction.
• C) PBC affects intrahepatic ducts only and presents with positive antimitochondrial antibodies.
• D) PSC affects intra- and extrahepatic ducts but is strongly linked with IBD and younger patients.
• E) Viral hepatitis causes hepatocellular pattern injury, not isolated cholestasis.

Educational Objective

Cholangiocarcinoma presents with painless jaundice and obstructive cholestatic liver enzyme pattern without gallstones.

Tutor Insight

Painless jaundice plus bile duct dilation without stones? Think tumor (cholangiocarcinoma) — not autoimmune or viral hepatitis.

Question 16 — Smoker with central lung mass producing PTHrP

Pulm/Onc

A 66-year-old man with a history of smoking presents with worsening cough and hemoptysis. Chest CT reveals a centrally located lung mass. Biopsy shows malignant cells producing parathyroid hormone–related peptide (PTHrP).

Which of the following electrolyte abnormalities is most likely in this patient?

1. Hypercalcemia
2. Hyperkalemia
3. Hypermagnesemia
4. Hypocalcemia
5. Hyponatremia

Answer: A) Hypercalcemia

Why this is correct

A central lung mass in a smoker with PTHrP production points toward squamous cell carcinoma of the lung. PTHrP mimics parathyroid hormone, leading to hypercalcemia by increasing bone resorption and renal calcium reabsorption. Hypercalcemia explains potential symptoms like fatigue, constipation, and confusion.

Why the others are wrong

• B) Hyperkalemia is not typical in paraneoplastic syndromes linked to squamous carcinoma.
• C) Hypermagnesemia is usually related to renal failure.
• D) Hypocalcemia would not result from PTHrP secretion.
• E) Hyponatremia is associated with SIADH (often in small cell carcinoma).

Educational Objective

Squamous cell carcinoma of the lung often produces PTHrP, leading to hypercalcemia of malignancy.

Tutor Insight

Centrally located lung mass + hypercalcemia = squamous cell carcinoma — SIADH and hyponatremia suggest small cell.

Question 17 — Fatigue and skin pigmentation with iron overload

GI/Hepato

A 44-year-old man presents with fatigue and new skin pigmentation.

Laboratory studies reveal:
Fasting blood glucose: 162 mg/dL
Serum iron: Elevated
Total iron-binding capacity: Low
Ferritin: Elevated

Which of the following is the most likely cause of his symptoms?

1. Chronic alcohol use
2. Hemochromatosis
3. Iron-deficiency anemia
4. Vitamin B12 deficiency
5. Wilson disease

Answer: B) Hemochromatosis

Why this is correct

Fatigue, hyperpigmentation, diabetes, and iron studies showing high serum iron, low TIBC, and high ferritin suggest hemochromatosis. Hereditary hemochromatosis is caused by mutations in the HFE gene, leading to excessive intestinal iron absorption.

Why the others are wrong

• A) Alcohol use elevates liver enzymes but doesn't cause hyperpigmentation or diabetes through iron overload.
• C) Iron deficiency would show low iron and high TIBC.
• D) B12 deficiency causes macrocytic anemia but not iron overload or pigmentation.
• E) Wilson disease involves copper accumulation, not iron.

Educational Objective

Hemochromatosis results in excessive iron accumulation, causing diabetes ("bronze diabetes"), skin pigmentation, and liver damage.

Tutor Insight

High iron, low TIBC, bronze skin, and diabetes? Hemochromatosis — not B12 deficiency or Wilson's copper overload.

Question 18 — Progressive dysphagia with bird-beak esophagus

GI

A 65-year-old man presents with progressive difficulty swallowing both solids and liquids. He has also lost 10 pounds over the past 2 months. Barium swallow shows a dilated esophagus with a bird-beak narrowing at the gastroesophageal junction. Manometry reveals absent peristalsis and increased lower esophageal sphincter (LES) tone.

Which of the following best explains the pathophysiology of this patient's condition?

1. Autoimmune destruction of smooth muscle cells
2. Degeneration of inhibitory neurons in the myenteric plexus
3. Gastroesophageal reflux leading to scarring
4. Loss of Auerbach plexus ganglion cells secondary to Chagas disease
5. Mechanical obstruction from distal esophageal tumor

Answer: B) Degeneration of inhibitory neurons in the myenteric plexus

Why this is correct

Dysphagia to both solids and liquids with bird-beak esophagus and absent peristalsis suggests achalasia. The primary defect in idiopathic achalasia is degeneration of inhibitory neurons (nitric oxide producing) in the myenteric (Auerbach) plexus, preventing LES relaxation.

Why the others are wrong

• A) Autoimmune destruction is not the primary mechanism.
• C) GERD typically causes dysphagia to solids first secondary to scarring, not absent peristalsis.
• D) Chagas disease can mimic achalasia but requires specific epidemiologic context.
• E) Mechanical obstruction would show normal peristalsis above the blockage initially.

Educational Objective

Achalasia is caused by degeneration of inhibitory neurons leading to incomplete LES relaxation and loss of esophageal peristalsis.

Tutor Insight

If you see bird-beak plus solid and liquid dysphagia? Think neuron degeneration (achalasia), not mechanical tumor block.

Question 19 — COPD patient with respiratory acidosis and elevated bicarbonate

Pulm

A 65-year-old man with chronic obstructive pulmonary disease (COPD) presents with increasing shortness of breath. He is afebrile.

Arterial blood gas:
pH: 7.31
PaCO₂: 60 mm Hg
PaO₂: 52 mm Hg
HCO₃⁻: 30 mEq/L

Which of the following best describes the acid-base disturbance?

1. Acute respiratory acidosis
2. Chronic respiratory acidosis with metabolic compensation
3. Metabolic acidosis with respiratory compensation
4. Mixed respiratory and metabolic acidosis
5. Respiratory alkalosis

Answer: B) Chronic respiratory acidosis with metabolic compensation

Why this is correct

Elevated PaCO₂ with low pH suggests respiratory acidosis. Elevated bicarbonate (HCO₃⁻) is consistent with renal compensation, meaning this is chronic respiratory acidosis rather than acute. Chronic hypercapnia from COPD is a classic cause.

Why the others are wrong

• A) Acute respiratory acidosis would have elevated CO₂ but little or no HCO₃⁻ compensation.
• C) Metabolic acidosis would have low HCO₃⁻.
• D) Mixed acidosis would show derangements in both respiratory and metabolic directions without compensation.
• E) Respiratory alkalosis would have low PaCO₂ and high pH.

Educational Objective

Chronic respiratory acidosis features elevated PaCO₂ with compensatory renal HCO₃⁻ retention to buffer the acidosis.

Tutor Insight

High CO₂ and high bicarbonate? That's compensated chronic respiratory acidosis — not acute without renal help.

Question 20 — Post-appendectomy fever with pelvic fluid collection

Surgery

A 24-year-old woman comes to the clinic with persistent right lower quadrant pain. She underwent appendectomy 2 weeks ago for a ruptured appendix. She now reports fevers and malaise. On examination, there is right lower quadrant tenderness. CT scan reveals a 5-cm fluid collection in the pelvis.

Which of the following is the best next step in management?

1. Administer oral broad-spectrum antibiotics
2. Immediate laparotomy
3. Image-guided percutaneous drainage
4. Repeat appendectomy
5. Surgical removal of necrotic bowel

Answer: C) Image-guided percutaneous drainage

Why this is correct

Fever, localized tenderness, and a fluid collection after surgery are consistent with a postoperative intra-abdominal abscess. Best management for a sizable abscess (>3 cm) is image-guided percutaneous drainage, often combined with antibiotics. Oral antibiotics alone are insufficient without source control.

Why the others are wrong

• A) Antibiotics alone would not resolve a large abscess.
• B) Laparotomy is unnecessary unless drainage fails or the patient is unstable.
• D) Repeat appendectomy is unnecessary after removal unless there's stump appendicitis, which is rare.
• E) Necrotic bowel resection is not indicated unless bowel ischemia or perforation is found.

Educational Objective

Postoperative abscesses are best managed with image-guided percutaneous drainage plus antibiotic therapy when feasible.

Tutor Insight

Post-op fever plus localized fluid? Drain it percutaneously — don't just throw antibiotics at a pus pocket.

Hard Questions (21–25)

Hard questions tend to be multi-step: you’ll need to identify the syndrome, choose the mechanism, and avoid tempting distractors. Treat these step 1 practice questions free like training for game day—slow down, justify every step, and review your misses carefully.

Question 21 — Traveler with profuse watery diarrhea and no blood

Infect/GI

A 50-year-old man who recently returned from a trip to Mexico presents with profuse watery diarrhea. He has no fever or blood in his stool. Stool studies show no leukocytes or red blood cells.

Which of the following best explains the pathogenesis of his diarrhea?

1. Cytokine-mediated intestinal inflammation
2. Destruction of intestinal villi
3. Enterotoxin-mediated chloride secretion
4. Invasion of intestinal mucosa
5. Toxin-mediated inactivation of EF-2

Answer: C) Enterotoxin-mediated chloride secretion

Why this is correct

Traveler's watery diarrhea without blood or leukocytes suggests secretory diarrhea, not invasive disease. Enterotoxigenic E. coli (ETEC) is a common cause and produces heat-labile and heat-stable enterotoxins, which stimulate chloride secretion via cAMP and cGMP, respectively. Increased chloride secretion draws water into the intestinal lumen.

Why the others are wrong

• A) Cytokine-mediated inflammation causes dysentery with leukocytes and blood.
• B) Villi destruction is seen in rotavirus or celiac disease, not acute traveler's diarrhea.
• D) Mucosal invasion causes bloody diarrhea (e.g., Shigella, Salmonella).
• E) Toxin inactivation of EF-2 is a feature of diphtheria toxin, not ETEC.

Educational Objective

Traveler's diarrhea is often caused by ETEC, which induces secretory diarrhea through toxin-mediated chloride and water secretion.

Tutor Insight

Watery runs abroad? ETEC pumps chloride flood — not invaders busting guts.

Question 22 — Infertile male with small testes and 47,XXY karyotype

Repro

A 32-year-old man presents with infertility. He has decreased facial hair growth, small testes, and gynecomastia.

Laboratory studies reveal:
Serum FSH: High
Serum LH: High
Serum testosterone: Low
Karyotype: 47, XXY

Which of the following best explains the pathogenesis of his infertility?

1. Defective androgen receptor signaling
2. Failure of Sertoli and Leydig cell function
3. Mutation in the SRY gene
4. Overproduction of inhibin B
5. Testicular torsion during adolescence

Answer: B) Failure of Sertoli and Leydig cell function

Why this is correct

Tall male with small testes, gynecomastia, and karyotype 47, XXY points directly to Klinefelter syndrome. Testicular atrophy is caused by degeneration of both Sertoli cells (responsible for inhibin B production) and Leydig cells (testosterone production), leading to infertility and low testosterone. High FSH and LH reflect loss of negative feedback from failing Sertoli and Leydig cells.

Why the others are wrong

• A) Defective androgen receptors cause androgen insensitivity syndrome, typically with 46, XY karyotype and female external genitalia.
• C) SRY gene mutations result in streak gonads, not small fibrotic testes.
• D) Inhibin B would be low, not high, with Sertoli cell failure.
• E) Testicular torsion can cause testicular atrophy but would not explain the chromosomal abnormality.

Educational Objective

Klinefelter syndrome (47, XXY) results in Sertoli and Leydig cell dysfunction, causing infertility, gynecomastia, and hypogonadism.

Tutor Insight

XXY + low T + empty sperm count? Klinefelter wrecks both Sertoli and Leydig — not androgen locks.

Question 23 — Hematuria and edema after sore throat with subepithelial humps

Renal

A 23-year-old man presents with hematuria, proteinuria, and lower extremity edema. Two weeks ago, he had a sore throat.

Laboratory studies reveal:
Serum creatinine: 2.0 mg/dL
Serum complement C3: Low
ASO titers: Elevated
Kidney biopsy: Subepithelial humps on electron microscopy

Which of the following best explains the glomerular injury?

1. Antiglomerular basement membrane antibody deposition
2. Immune complex deposition
3. Linear deposition of complement
4. Podocyte effacement
5. T-cell–mediated podocyte injury

Answer: B) Immune complex deposition

Why this is correct

Recent streptococcal infection followed by nephritic syndrome (hematuria, edema) suggests poststreptococcal glomerulonephritis (PSGN). PSGN is mediated by immune complex deposition, forming subepithelial "humps" seen on electron microscopy.

Why the others are wrong

• A) Anti-GBM disease (Goodpasture's) shows linear IgG deposition, not granular.
• C) Linear complement deposition is not characteristic; immune complexes trigger complement activation.
• D) Podocyte effacement is seen in minimal change disease, causing nephrotic syndrome.
• E) T-cell injury underlies minimal change disease, not PSGN.

Educational Objective

Poststreptococcal glomerulonephritis is caused by immune complex deposition and presents with low C3, elevated ASO titers, and subepithelial humps.

Tutor Insight

Strep throat → puffy pee = humps of immune junk — not sleek podocyte slides.

Question 24 — HIV patient with seizures and ring-enhancing brain lesions

Infect/Neuro

A 29-year-old woman with HIV (CD4 count 35/mm³) presents with new onset seizures. MRI of the brain shows multiple ring-enhancing lesions in the basal ganglia. Serologic testing reveals positive Toxoplasma IgG.

Which of the following is the most appropriate initial therapy?

1. Amphotericin B
2. Ceftriaxone and vancomycin
3. Pyrimethamine, sulfadiazine, and leucovorin
4. Trimethoprim-sulfamethoxazole
5. Valganciclovir

Answer: C) Pyrimethamine, sulfadiazine, and leucovorin

Why this is correct

HIV with CD4 <100 and multiple ring-enhancing lesions highly suggests Toxoplasma encephalitis. Positive Toxoplasma IgG is consistent with reactivation. First-line treatment is pyrimethamine plus sulfadiazine and leucovorin (to prevent bone marrow toxicity).

Why the others are wrong

• A) Amphotericin B treats cryptococcal meningitis, not Toxoplasma.
• B) Ceftriaxone and vancomycin treat bacterial meningitis.
• D) TMP-SMX is used for prophylaxis, not active CNS toxoplasmosis.
• E) Valganciclovir treats CMV infections, not Toxoplasma.

Educational Objective

CNS toxoplasmosis in AIDS patients is treated with pyrimethamine, sulfadiazine, and leucovorin.

Tutor Insight

Ring brain bugs + HIV drop? Pyrimethamine trio strikes Toxo — not TMP rescue.

Question 25 — Prosthetic valve endocarditis with pulmonary edema

Cardio

A 45-year-old woman with a mechanical mitral valve replacement presents with fever and new-onset shortness of breath. On examination, she has a new holosystolic murmur at the apex. Blood cultures are positive for Staphylococcus epidermidis. Echocardiogram reveals vegetations on the mitral valve and evidence of pulmonary edema.

Which of the following best explains her pulmonary findings?

1. Acute mitral valve regurgitation
2. Acute tricuspid valve regurgitation
3. Mitral stenosis
4. Pulmonary embolism
5. Right ventricular failure

Answer: A) Acute mitral valve regurgitation

Why this is correct

New murmur and vegetations on a prosthetic mitral valve strongly suggest infective endocarditis leading to acute mitral regurgitation. Mitral regurgitation causes increased left atrial pressure, backing up into the pulmonary circulation, resulting in pulmonary edema.

Why the others are wrong

• B) Tricuspid regurgitation leads to systemic congestion, not pulmonary edema.
• C) Mitral stenosis causes chronic pulmonary congestion, not sudden pulmonary edema.
• D) Pulmonary embolism causes ventilation-perfusion mismatch, not murmur-related pulmonary edema.
• E) Right heart failure would cause peripheral, not pulmonary, edema.

Educational Objective

Acute mitral regurgitation secondary to infective endocarditis leads to sudden pulmonary edema from backward pressure overload.

Tutor Insight

Valves veg + breath flood? Mitral rupture surges — not tricuspid slip or lung clots.

Study Tips: How to Get the Most Out of Practice Questions

Want these USMLE Step 1 sample questions to translate into a higher score? Use this simple workflow:

1. Do questions timed (even early).
   Start with small sets (10–15) to build pace without burning out.

2. Review explanations like you’re building flashcards.
   For every miss, write down: What clue I missed + What rule would have made this easy next time.

3. Track patterns, not just topics.
   Many Step 1 misses come from repeat traps (e.g., confusing similar presentations, misreading iron studies, mixing up compensation rules).

4. Re-do your incorrect strategically.
   After 5–7 days, redo missed questions to confirm the concept stuck.

5. Mix difficulty on purpose.
   Use easy questions to build confidence and speed, medium questions to sharpen reasoning, and hard questions to practice multi-step integration.

If you’re searching for step 1 practice questions free, this page is a great starting point—but consistent, targeted review is what turns “practice” into points.

Turn Practice into Points

High-quality USMLE Step 1 practice questions are one of the best ways to improve—especially when you review them with intention. Keep working through USMLE Step 1 example questions, learn the recurring patterns, and make your mistakes early (so you don’t make them on test day).

If you want a personalized study plan, accountability, and high-yield coaching tailored to your weaknesses, MedBoardTutors offers 1-on-1 tutoring with licensed physician tutors who scored 260+.

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