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Background The emergency department (ED) is a stressful clinical environment. Stress activates the sympathetic nervous system (SNS), which leads to physiologic responses such as an increase in heart rate (HR) and heart rate variability (HRV). Studies have shown a relationship between HRV and cognitive performance. As a training tool, simulation attempts to mimic real-world conditions, including the reproduction of physiologic stress reactions in learners. Objectives In this pilot study, we sought to assess the physiologic indicators of resident stress induced by simulation, whether measurement of these parameters was feasible during simulation, and whether this stimulation during simulation would lead to cognitive performance improvements. Methods A wearable device was used to measure HR, HRV, and electrodermal activity (EDA) at two American College of Graduate Medical Education (ACGME) accredited emergency medicine (EM) residency programs during a simulation scenario. All residents at the participating sites were eligible to participate. A standardized simulation protocol was utilized. Before and during the scenario, participants completed a cognitive test, and the time of completion was noted. We calculated and reported descriptive statistics on HR, HRV, and EDA. For the IBI data, HRV was also analyzed using three methods: standard deviation, root mean square of successive differences, and PNN50. Results Twenty-six residents participated, including 7 postgraduate year 1 (PGY1), 8 PGY2, and 11 PGY3. Further, 11 (42.3%) participants were females, 15 (57.7%) were male, and the mean age was 30.7 years. The mean HR range was 59.11–117.46. The average percentages of time the HR was above 120, 130, and >160 were 2.475, 0.88, and 0.041%, respectively. HRV showed that the mean standard deviation of the interbeat interval (IBI) was 87 ms. EDA showed a trend toward increasing throughout the scenario. Conclusions In this pilot study, simulation-induced physiologic indications of stress were observed as evidenced by increased HR, HRV, and EDA. Measurement of these parameters was feasible and can help to tailor simulation for maximum educational effectiveness. Cognitive testing performance showed improvement in time to completion.