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Psychological risk factors are increasingly recognized as important in sport-related injury prevention. Understanding how these psychological factors may affect the risk of injuries could help design effective prevention programs.To determine the effect of reported preseason anxiety and depressive symptoms on the risk of injuries during a prospective season in a cohort of collegiate athletes.Cohort study; Level of evidence, 2.Collegiate athletes participating in 4 men’s sports and 5 women’s sports from 2 National Collegiate Athletic Association (NCAA) Division I universities were enrolled and prospectively followed during the 2007-2011 seasons. Preseason anxiety and depressive symptoms were measured at enrollment. Injuries occurring during the season were reported by certified athletic trainers. The injury incidence rate was calculated as the total number of injuries divided by the total number of athlete-exposures (ie, games and practices).Of 958 enrolled athletes (response rate of 90.3%), 389 (40.6%) athletes sustained a total of 597 injuries. At preseason, 276 (28.8%) athletes reported anxiety symptoms, and 208 (21.7%) reported depressive symptoms. Among athletes reporting any of these symptoms, 48.5% (n = 158) reported having both anxiety and depressive symptoms. Athletes with preseason anxiety symptoms had a significantly higher injury incidence rate compared with athletes without anxiety symptoms (rate ratio [RR], 2.3; 95% CI, 2.0-2.6), adjusting for age, race, body mass index, history of injuries 12 months before baseline, and university attended, and this was observed for both male and female athletes. Only male athletes who reported co-occurring preseason depressive and anxiety symptoms had a significantly increased injury risk (RR, 2.1; 95% CI, 1.6-2.6) compared with male athletes who reported no co-occurring symptoms. However, no such increase in the injury risk was observed among female athletes or male athletes who reported preseason depressive symptoms but no anxiety symptoms.Athletes with anxiety symptoms at preseason were at an increased risk of injuries during the prospective season. Targeted programs could focus on psychological health and injury prevention for athletes, especially for those exhibiting symptoms at preseason.