The USMLE program does not release past papers — it publishes question formats and sample items instead. So the useful thing a practice page can do is show the shape of reasoning a Step 1 vignette demands, and how to review an attempt. The ten questions below are from the Myndaq Step 1 practice bank, each with the reasoning for the right answer and the wrong ones, alongside the Myndaq USMLE Step 1 course.
The pattern you are practising against
- Fourteen 30-minute blocks, in one 8-hour testing session, for exams taken on or after 14 May 2026.
- No more than 20 questions per block, though the number may vary between forms.
- A minimum of 55 minutes of break time, plus a 5-minute optional tutorial, within that session.
- Single best answer, with more options than the four or five a typical undergraduate paper uses — you are eliminating, not recognising.
- No negative marking is published: the outcome is a recommended pass or fail against a specified proficiency standard, and no predetermined percentage of examinees passes or fails. An unanswered question cannot score, so a reasoned guess is never worse than a blank.
Thirty minutes for up to twenty questions is roughly 90 seconds per item. The older seven-block structure let you bank time across a whole hour; a 30-minute block does not forgive a five-minute stall on question three.
Work the questions under time before reading any explanation. For each one you get wrong — and each one you get right for the wrong reason — write down the single clue in the stem that should have driven the answer. Ten items reviewed until you can name the distractor you fell for beats a hundred skimmed.
Ten worked questions
1. Bias in a cross-sectional survey
A cross-sectional survey of 10,000 adults finds that individuals with diabetes have a much lower prevalence of severe emphysema than nondiabetics, suggesting diabetes is "protective." Investigators note that patients with both severe emphysema and diabetes die at very high rates and are therefore underrepresented among survivors available for the survey. Which type of bias best explains the spurious inverse association?
- A. Berkson (admission-rate) bias
- B. Confounding by indication
- C. Survivorship (selective survival) bias
- D. Recall bias
- E. Lead-time bias
Answer: C. Because those with both conditions die and drop out of the survivable population, the sample selectively retains survivors, producing a falsely protective association. Lead-time bias applies to screening survival comparisons; recall bias to retrospective exposure reporting; Berkson bias to differential hospital admission; confounding by indication to treatment given on prognosis. None describe selective mortality removing subjects before measurement.
2. Why an antidote's timing matters
A 34-year-old man is found unconscious. His pupils are 2 mm and pinpoint, respiratory rate is 6/min, and he has diffuse muscle fasciculations, profuse salivation, lacrimation, urinary incontinence and diarrhoea. Blood testing shows markedly decreased red-cell acetylcholinesterase activity. In addition to atropine, pralidoxime is administered. Why must pralidoxime be given promptly rather than delayed?
- A. The agent covalently modifies nicotinic receptors, which pralidoxime can regenerate only within minutes
- B. Over time the inhibited enzyme undergoes "aging," losing an alkyl group and becoming resistant to reactivation by the oxime
- C. Pralidoxime inhibits butyrylcholinesterase, which is only transiently elevated after exposure
- D. Delay permits hepatic conversion of the agent to a more potent oxon metabolite that pralidoxime cannot bind
- E. Pralidoxime blocks muscarinic receptors, and delay allows irreversible receptor downregulation
Answer: B. This is an organophosphate toxidrome. Pralidoxime regenerates acetylcholinesterase by displacing the phosphate group, but after "aging" — loss of an alkyl side group from the phosphorylated enzyme — the bond becomes irreversible and the oxime is ineffective. Pralidoxime does not block muscarinic receptors (atropine's role) or act clinically on butyrylcholinesterase.
3. An inborn error with a normal gene sequence
A 3-week-old boy who missed newborn screening develops vomiting, lethargy and progressive intellectual disability. He has fair skin, blue eyes and a musty odour. Blood phenylalanine is markedly elevated with low tyrosine, and his phenylalanine hydroxylase gene sequence is normal. Which enzymatic reaction is most directly deficient in classic (non-cofactor) forms of this disease?
- A. Conversion of methionine to homocysteine
- B. Hydroxylation of phenylalanine to tyrosine
- C. Conversion of homogentisate to maleylacetoacetate
- D. Oxidative decarboxylation of branched-chain ketoacids
- E. Transamination of tyrosine
Answer: B. Phenylketonuria results from impaired hydroxylation of phenylalanine to tyrosine, by phenylalanine hydroxylase or its BH4 cofactor. Homogentisate defects cause alkaptonuria; branched-chain ketoacid decarboxylation defects cause maple syrup urine disease; methionine-to-homocysteine steps relate to transsulfuration.
4. The cell doing the damage
A 28-year-old woman presents with fatigue, Raynaud phenomenon and progressive tightening of the skin over her fingers and face, with difficulty swallowing. Anti-topoisomerase I (Scl-70) antibodies are present. Skin biopsy shows excessive collagen deposition in the dermis with vascular intimal proliferation. Which cell type is most directly responsible for the excessive matrix deposition?
- A. Endothelial progenitor cell
- B. Neutrophil
- C. Fibroblast
- D. Osteoclast
- E. Plasma cell
Answer: C. Diffuse systemic sclerosis is characterised by fibroblast activation, driven by TGF-β and PDGF, producing excessive collagen and matrix. Osteoclasts resorb bone; neutrophils mediate acute inflammation, not fibrosis; plasma cells make the autoantibodies but lay down no collagen; and while endothelial injury drives the vasculopathy, endothelial progenitor cells are not the effectors of matrix deposition.
5. Localising a lacunar stroke
A 68-year-old woman with hypertension and diabetes develops sudden dense weakness and complete sensory loss of the right face, arm and leg, with no aphasia, no neglect and no visual field deficit. MRI shows a small lacunar infarct. Occlusion of small penetrating branches supplying which structure best explains this presentation?
- A. Cerebellar hemisphere
- B. Lateral surface of the parietal cortex
- C. Occipital cortex
- D. Broca area in the inferior frontal gyrus
- E. Posterior limb of the internal capsule and adjacent thalamus
Answer: E. Pure sensorimotor stroke without cortical signs is the classic lacunar syndrome, from lipohyalinosis of lenticulostriate or thalamoperforator vessels affecting the internal capsule and adjacent thalamus, where motor and sensory fibres run densely packed. Broca and lateral parietal lesions would give aphasia or neglect, occipital lesions a field cut, cerebellar lesions ataxia. The absence of cortical signs is the clue.
6. A cofactor given before glucose
A 55-year-old man with chronic alcohol use disorder presents with confusion, ataxia and horizontal gaze palsy. He is given a vitamin before any dextrose-containing fluids. Deficiency of the cofactor derived from this vitamin most directly impairs which enzyme?
- A. Alpha-ketoglutarate dehydrogenase
- B. Glucose-6-phosphate dehydrogenase
- C. Homocysteine methyltransferase
- D. Methylmalonyl-CoA mutase
- E. Prolyl hydroxylase
Answer: A. Wernicke encephalopathy reflects thiamine deficiency; thiamine pyrophosphate is a cofactor for alpha-ketoglutarate dehydrogenase, pyruvate dehydrogenase and transketolase. Methylmalonyl-CoA mutase and homocysteine methyltransferase depend on B12 and folate, G6PD on NADP+, prolyl hydroxylase on vitamin C.
7. Reading a volume of distribution
A highly lipophilic drug has an apparent volume of distribution of 700 L in a 70-kg adult. What best explains a volume of distribution far exceeding total body water (~42 L)?
- A. Confinement of the drug to the plasma compartment
- B. High plasma protein binding retaining drug in blood
- C. Extensive sequestration of drug in peripheral tissues
- D. Poor oral bioavailability of the drug
- E. Rapid renal clearance of the drug
Answer: C. Volume of distribution relates total drug in the body to plasma concentration. A value far above body water means drug is sequestered in peripheral tissues, lowering measured plasma concentration. Plasma confinement or high protein binding would keep drug in blood and give a small Vd; clearance and bioavailability describe elimination and absorption, not distribution.
8. A classic interaction
A 60-year-old man with severe reflux oesophagitis is treated with cimetidine and remains on chronic warfarin and phenytoin. His physician notes that cimetidine can raise levels of both drugs. Which mechanism explains this?
- A. Increased gastric pH reducing drug absorption
- B. Inhibition of hepatic cytochrome P450 enzymes
- C. Inhibition of renal tubular secretion of both drugs
- D. Displacement of drugs from plasma albumin
- E. Induction of hepatic cytochrome P450 enzymes
Answer: B. Cimetidine inhibits several cytochrome P450 isoenzymes, decreasing metabolism of warfarin and phenytoin and raising their serum levels. Induction would lower levels; albumin displacement, renal secretion inhibition and altered gastric absorption do not account for cimetidine's characteristic enzyme-inhibition interactions.
9. Naming a hypersensitivity subtype
A 32-year-old woman presents with fatigue, tachycardia and heat intolerance. She has a diffuse goitre and elevated thyroid uptake. Serum contains an IgG antibody that binds the thyrotropin (TSH) receptor and continuously stimulates it. Which hypersensitivity mechanism best characterises this disease?
- A. Type II: antibody-mediated complement lysis of thyrocytes
- B. Type IV: T-cell-mediated delayed cytotoxicity
- C. Type III: immune complex deposition and complement activation
- D. Type II: antibody binding a cell-surface receptor and altering its function
- E. Type I: IgE-mediated mast cell degranulation
Answer: D. Graves disease is a type II reaction in which a stimulatory IgG autoantibody binds the TSH receptor and mimics ligand, driving hormone overproduction without destroying the cell. A and D are both type II: the question tests the distinction between the destructive and the function-altering subtype. Two options sharing a label is a common Step 1 construction.
10. Disclosing an error
A first-year resident inadvertently orders a tenfold overdose of an antihypertensive, and the patient develops symptomatic hypotension requiring a brief ICU stay before recovering fully. The attending is deciding how to communicate with the patient. Which approach to disclosure is most appropriate?
- A. Withhold disclosure because the patient recovered fully and no lasting harm occurred
- B. Attribute the outcome to the patient's underlying illness to preserve trust in the care team
- C. Disclose only if the patient specifically asks whether an error occurred
- D. Delay any conversation until the hospital's legal counsel has fully reviewed liability exposure
- E. Promptly disclose the error, explain what happened, express sincere apology, and describe steps to prevent recurrence
Answer: E. Contemporary patient-safety and ethics standards require prompt, truthful disclosure, an authentic apology and an explanation of corrective action. Withholding because harm resolved, delaying for liability review, disclosing only on request, or misattributing the outcome all violate the duty of honesty. Communication and professionalism items reward the candid, patient-centred answer, not the cautious institutional one.
Turning attempts into marks
Three patterns above generalise.
The distinguishing clue is often a negative. Question 5 is solved by what the patient does not have. Read absent findings as data.
Two options may share a label. Question 9 offers type II twice: when two options carry the same heading, the examined point is the distinction between them.
Mechanism questions want the step, not the disease. Questions 2, 3, 6 and 8 name the condition freely and then ask about one reaction. Recognising the disease scores nothing on its own.
For how the exam is specified, see the USMLE Step 1 syllabus and content outline. For cost, eligibility and attempt limits, see USMLE Step 1 fees and registration.
Quick answers
Does the USMLE release past papers?
No. The USMLE program publishes question formats and official sample items and practice materials rather than retired papers, so any "past paper" offered elsewhere is not an official release.
How long do I get per question?
For exams on or after 14 May 2026, blocks are 30 minutes with no more than 20 questions, which is about 90 seconds per item.
Is there negative marking on Step 1?
No deduction for a wrong answer is published; the outcome is a recommended pass or fail set against a proficiency standard. Since a blank cannot score, an eliminated-then-reasoned guess is always preferable to leaving an item unanswered.
How many practice questions should I do?
The count matters far less than the review. A question you can explain — including why each distractor was written — is worth many you have merely seen.
