OBJECTIVE: Given concerns about the potential long-term effects of concussion in young athletes, concussion prevention has become a major focus for amateur sports leagues. Athletes have been known to frequently use anti-inflammatory medications to manage injuries, expedite return to play, and treat concussion symptoms. However, the effects of baseline nonsteroidal anti-inflammatory drug (NSAID) use on the susceptibility to head injury and concussion remain unclear. This study aims to assess the effects of preinjury NSAID use on concussion incidence, severity, and recovery in young athletes. METHODS: Data from 25,815 ImPACT (Immediate Post-Concussion Assessment and Cognitive Testing) tests were obtained through a research agreement with ImPACT Applications Inc. Subjects ranged in age from 12 to 22 years old. Those who reported NSAID use at baseline were assigned to one (anti-inflammatory [AI]) cohort, whereas all others were assigned to the control (CT) cohort. Differences in head trauma and concussion incidence, severity, and recovery were assessed using chi-square tests, unpaired t-tests, and Kaplan-Meier plots. RESULTS: The CT cohort comprised a higher percentage (p < 0.0001) of males (66.30%) than the AI cohort (44.16%) and had a significantly greater portion of athletes who played football (p = 0.004). However, no statistically significant differences were found between the two cohorts in terms of the incidence of head trauma (CT = 0.489, AI = 0.500, p = 0.9219), concussion incidence (CT = 0.175, AI = 0.169, p = 0.7201), injury severity, or median concussion recovery time (CT = 8, AI = 8, p = 0.6416). In a multivariable analysis controlling for baseline differences between the cohorts, no association was found between NSAID use and concussion incidence or severity. CONCLUSIONS: In this analysis, the authors found no evidence that preinjury use of NSAIDs affects concussion risk in adolescent athletes. They also found no indication that preinjury NSAID use affects the severity of initial injury presentation or concussion recovery.