Youth athletes are beginning to specialize in a single sport more often. Previous studies in sports medicine and orthopedics have shown an association between intensity of sport specialization and incidence of injuries. This study is the first of its kind to explore the effects of early sport specialization on injury risk through a multicenter framework with a concentration on NCAA athletics. Retrospective cohort study. SAFE Consortium. A total of 211 collegiate athletes from the NCAA's 3 levels of competition: Division I, II, and III. Data were collected by the SAFE investigators. N/A. Participants completed a questionnaire about their demographics, sport participation, specialization status, physical injuries, recovery period, and treatment method. Specialization status was calculated with a previously published 3-point scale: low, moderate, and high. Injuries were categorized as upper extremity injuries (UEIs) and lower extremity injuries (LEIs). Highly specialized athletes were more likely to report UEIs and LEIs than low specialized athletes (P < 0.0001). Moderate specialization, in contrast to low specialization, was associated with a higher likelihood of LEIs (P = 0.03) but not UEIs (P = 0.052). Highly specialized athletes were more likely to report an injury of any kind. The SAFE investigators found high specialization was associated with a history of UEIs and LEIs. Return to play was longer for highly specialized athletes versus low specialized athletes (112 days and 85 days, respectively). Highly specialized athletes were more likely to be from Division I and to require surgery.