To assess the effect of a neuromuscular training program on the incidence of anterior cruciate ligament (ACL) injuries in female team handball athletes, a prospective intervention study of female team handball athletes from divisions I, II, and III in Norway was conducted. The control season (1998-1999) included 60 teams (942 athletes), the first intervention season (1999-2000) included 58 teams (855 athletes), and the second intervention season (2000-2001) included 52 teams (850 athletes). For the intervention teams, a five-phase program (duration, 15 minutes) with three different balance exercises focusing on neuromuscular control and planting and landing skills was developed and introduced to the athletes in the autumn of 1999 and revised before the start of the season in 2000. Each intervention team was instructed in the program and supplied with an instructional video, poster, six balance mats, and six wobble boards. Additionally, a physical therapist was assigned to each team for follow-up during the second intervention season. The number of ACL injuries during the three seasons and compliance with the program were assessed. Twenty-nine ACL injuries occurred during the control season, 23 during the first intervention season (odds ratio [OR], 0.87 [0.50-1.52]; P = 0.62), and 17 during the second intervention season (OR, 0.64 [0.35-1.18]; P = 0.15). In the elite division, 13 injuries occurred during the control season, 6 during the first intervention season (OR, 0.51 [0.19-1.35]; P = 0.17), and 5 during the second intervention season (OR, 0.37 [0.13-1.05]; P = 0.06). For the entire cohort, no difference in injury rates was noted during the second intervention season between compliers and noncompliers (OR, 0.52 [0.15-1.82], P = 0.31). In the elite division, the risk of injury was reduced among athletes who completed the ACL injury prevention program (OR, 0.06 [0.01-0.54], P = 0.01) compared with those who did not. The results demonstrate that it is possible to prevent ACL injuries with specific neuromuscular training.