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To determine whether full-scale simulation (SIM) is superior to interactive problem-based learning (PBL) for teaching medical students acute care assessment and management skills.Randomized controlled trial.Simulation center at a U.S. medical school.Thirty-one fourth-year medical students in a weeklong acute care course.After institutional review board approval and informed consent, eligible students were randomized to either the SIM or PBL group. On day 1, all subjects underwent a simulator-based initial assessment designed to evaluate their critical care skills. Two blinded investigators assessed each student using a standardized checklist. Subsequently, the PBL group learned about dyspnea in a standard PBL format. The SIM group learned about dyspnea using the simulator. To equalize simulator education time, the PBL group learned about acute abdominal pain on the simulator, whereas the SIM group used the PBL format. On day 5, each student was tested on a unique dyspnea scenario.Mean initial assessment and final assessment checklist scores and their change for the SIM and PBL groups were compared using the Student’s t-test. A p < .05 was considered significant. The SIM and PBL groups had similar mean (PBL 0.44, SIM 0.47, p = .64) initial assessment scores (earned score divided by maximum score) and were deemed equivalent. The SIM group performed better than the PBL group on the final assessment (mean, PBL 0.53, SIM 0.72, p < .0001). When each student’s change in score (percent correct on final assessment minus percent correct on the initial assessment) was compared, SIM group students performed better (mean improvement, SIM 25 percentage points vs. PBL 8 percentage points, p < .04)For fourth-year medical students, simulation-based learning was superior to problem-based learning for the acquisition of critical assessment and management skills.