Introduction:The occurrence of disasters and mass casualty incidents (MCIs) is on the rise, thus training and rehearsal for disaster response remain paramount. Virtual reality (VR) platforms have previously been shown to be well-received, engaging, and immersive for disaster training. The primary objective of this study was to ascertain if a human actor-based VR MCI scenario could elicit a sympathetic response, as measured by heart rate variability (HRV), in medical doctors and trainees compared to a baseline state.Method:A simulation was filmed with students, residents, and surgeons on a GoPro 360 camera. Subjects (n=35) were recruited to sufficiently power (1-b=0.8) a Wilcoxon matched-pairs test and Welch’s t-test. Subjects watched the simulation on an Oculus Quest headset while having HRV recorded. Multivariate logistic regression was performed to identify factors associated with increased odds of significant sympathetic activation. Statistical significance was established at p<0.05.Results:Thirty-five subjects were enrolled and included three trauma surgeons, three emergency medicine (EM) attendings, eight EM residents, six surgery residents, and 15 medical students. A significant decrease in HRV was observed across all groups in the MCI (median 20 ms IQR 16.2, 31.4 ms) compared to baseline (33.2 ms IQR 27.2, 44.1 ms; p<0.0001). Sympathetic activation was most pronounced in students, then attendings, then residents. There was no significant difference in the fold-difference of sympathetic activation of EM physicians (-48.5% +/- 32.1%) versus surgeons (-49.5% +/- 25.2%; p=0.57). In all groups, SNS activation occurred independently of heart rate, age, sex, number of years in practice, first responder experience, or prior MCI response.Conclusion:Live-actor VR MCI simulation elicited a strong sympathetic response from students, residents, and attending physicians. By recruiting and disinhibiting essential neural pathways via controlled SNS activation, VR MCI training has the potential to enhance the encoding and consolidation of disaster training in a low-cost and reproducible manner.