BACKGROUND: Simulation-based training is useful in improving physicians' skills. However, no randomized controlled trials have been able to demonstrate the effects of simulation teaching in real-life patient care. This study aimed to determine whether simulation-based training or an interactive seminar resulted in better patient care during weaning from cardiopulmonary bypass (CPB)-a high stakes clinical setting. METHODS: This study was conducted as a prospective, single-blinded, randomized controlled trial. After institutional research board approval, 20 anesthesiology trainees, postgraduate year 4 or higher, inexperienced in CPB weaning, and 60 patients scheduled for elective coronary artery bypass grafting were recruited. Each trainee received a teaching syllabus for CPB weaning 1 week before attempting to wean a patient from CPB (pretest). One week later, each trainee received a 2-h training session with either high-fidelity simulation-based training or a 2-h interactive seminar. Each trainee then weaned patients from CPB within 2 weeks (posttest) and 5 weeks (retention test) from the intervention. Clinical performance was measured using the validated Anesthesiologists' Nontechnical Skills Global Rating Scale and a checklist of expected clinical actions. RESULTS: Pretest Global Rating Scale and checklist performances were similar. The simulation group scored significantly higher than the seminar group at both posttest (Global Rating Scale [mean +/- standard error]: 14.3 +/- 0.41 vs. 11.8 +/- 0.41, P < 0.001; checklist: 89.9 +/- 3.0% vs. 75.4 +/- 3.0%, P = 0.003) and retention test (Global Rating Scale: 14.1 +/- 0.41 vs. 11.7 +/- 0.41, P < 0.001; checklist: 93.2 +/- 2.4% vs. 77.0 +/- 2.4%, P < 0.001). CONCLUSION: Skills required to wean a patient from CPB can be acquired through simulation-based training. Compared with traditional interactive seminars, simulation-based training leads to improved performance in patient care by senior trainees in anesthesiology.