Context: Prevention of a lower extremity sprain or strain requires some basis for predicting that an individual athlete will sustain such an injury unless a modifiable risk factor is addressed. Objective: To assess the possible existence of an association between reaction time measured during completion of a computerized neurocognitive test battery and subsequent occurrence of a lower extremity sprain or strain. Design: Prospective cohort study. Setting: Preparticipation screening conducted in a computer laboratory on the day prior to initiation of preseason practice sessions. Participants: 76 NCAA Division I-FCS football players. Main Outcome Measures: Lower extremity sprains and strains sustained between initiation of preseason practice sessions and the end of an 11-game season. Receiver operating characteristic analysis identified the optimal reaction time cut-point for discrimination between injured versus noninjured status. Stratified analyses were performed to evaluate any differential influence of reaction time on injury incidence between starters and nonstarters. Results: A total of 29 lower extremity sprains and strains were sustained by 23 of the 76 players. A reaction time cut-point of >= .545 s provided good discrimination between injured and noninjured cases: 74 % sensitivity, 51 % specificity, relative risk = 2.17 (90 % CI: 1.10, 4.30), and odds ratio = 2.94 (90 % CI: 1.19, 7.25). Conclusions: Neurocognitive reaction time appears to be an indicator of elevated risk for lower extremity sprains and strains among college football players, which may be modifiable through performance of exercises designed to accelerate neurocognitive processing of visual input.