Background High-fidelity simulation improves participant learning through immersive participation in a stressful situation. Stress management training might help participants to improve performance. The hypothesis of this work was that Tactics to Optimize the Potential, a stress management program, could improve resident performance during simulation. Methods Residents participating in high-fidelity simulation were randomized into two parallel arms (Tactics to Optimize the Potential or control) and actively participated in one scenario. Only residents from the Tactics to Optimize the Potential group received specific training a few weeks before simulation and a 5-min reactivation just before beginning the scenario. The primary endpoint was the overall performance during simulation measured as a composite score (from 0 to 100) combining a specific clinical score with two nontechnical scores (the Ottawa Global Rating Scale and the Team Emergency Assessment Measure scores) rated for each resident by four blinded independent investigators. Secondary endpoints included stress level, as assessed by the Visual Analogue Scale during simulation. Results Of the 134 residents randomized, 128 were included in the analysis. The overall performance (mean ± SD) was higher in the Tactics to Optimize the Potential group (59 ± 10) as compared with controls ([54 ± 10], difference, 5 [95% CI, 1 to 9]; P = 0.010; effect size, 0.50 [95% CI, 0.16 to 0.91]). After specific preparation, the median Visual Analogue Scale was 17% lower in the Tactics to Optimize the Potential group (52 [42 to 64]) than in the control group (63 [50 to 73]; difference, −10 [95% CI, −16 to −3]; P = 0.005; effect size, 0.44 [95% CI, 0.26 to 0.59]. Conclusions Residents coping with simulated critical situations who have been trained with Tactics to Optimize the Potential showed better overall performance and a decrease in stress level during high-fidelity simulation. The benefits of this stress management training may be explored in actual clinical settings, where a 5-min Tactics to Optimize the Potential reactivation is feasible prior to delivering a specific intervention. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New