OBJECTIVE: To examine the effectiveness of a sport-specific balance training program in reducing injury in adolescent basketball. DESIGN: Cluster randomized controlled trial. SETTING: Twenty-five high schools in Calgary and surrounding area. SUBJECTS: Nine hundred and twenty high school basketball players (ages 12-18). INTERVENTION: Subjects were randomly allocated by school to the control (n = 426) and training group (n = 494). Both groups were taught a standardized warm-up program. The training group was also taught an additional warm-up component and a home-based balance training program using a wobble board. MAIN OUTCOME MEASURES: All injuries occurring during basketball that required medical attention and/or caused a player to be removed from that current session and/or miss a subsequent session were then recorded and assessed by a team therapist who was blinded to training group allocation. RESULTS: A basketball-specific balance training program was protective of acute-onset injuries in high school basketball [RR = 0.71 (95% CI; 0.5-0.99)]. The protective effect found with respect to all injury [RR = 0.8 (95% CI; 0.57-1.11)], lower-extremity injury [RR = 0.83 (95% CI; 0.57-1.19)], and ankle sprain injury [RR = 0.71 (95% CI; 0.45-1.13)] were not statistically significant. Self-reported compliance to the intended home-based training program was poor (298/494 or 60.3%). CONCLUSIONS: A basketball-specific balance training program was effective in reducing acute-onset injuries in high school basketball. There was also a clinically relevant trend found with respect to the reduction of all, lower-extremity, and ankle sprain injury. Future research should include further development of neuromuscular prevention strategies in addition to further evaluation of methods to increase compliance to an injury-prevention training program in adolescents.