In this study, we hypothesized that immersive virtual reality (VR) environments may reduce pain in patients with acute traumatic injuries, including traumatic brain injuries. We performed a randomized within-subject study in patients hospitalized with acute traumatic injuries, including traumatic brain injury with moderate pain (numeric pain score ≥3 of 10). We compared 3 conditions: (1) an immersive VR environment (VR Blu), (2) a content control with the identical environment delivered through nonimmersive tablet computer (Tablet Blu), and (3) a second control composed of donning VR headgear without content to control for placebo effects and sensory deprivation (VR Blank). We enrolled 60 patients, and 48 patients completed all 3 conditions. Objective and subjective data were analyzed using linear mixed-effects models. Controlling for demographics, baseline pain, and injury severity, we found differences by conditions in relieving pain (F 2,75.43 = 3.32, P = 0.042). VR Blu pain reduction was greater than Tablet Blu (-0.92 vs -0.16, P = 0.043), but VR Blu pain reduction was similar to VR Blank (-0.92 vs -1.24, P = 0.241). VR Blu was perceived as most effective by patients for pain reduction (F 2,66.84 = 16.28, P < 0.001), and changes in measures of parasympathetic activity including heart rate variability (F 2,55.511 = 7.87, P < 0.001) and pupillary maximum constriction velocity (F 2,61.41 = 3.50, 1-tailed P = 0.038) echoed these effects. There were no effects on opioid usage. These findings outlined a potential clinical benefit for mollifying pain related to traumatic injuries. Copyright © 2023 International Association for the Study of Pain.