BACKGROUND: Soccer is a leading sport for participation and injury in youth. OBJECTIVE: To examine the effectiveness of a neuromuscular prevention strategy in reducing injury in youth soccer players. DESIGN: Cluster-randomised controlled trial. SETTING: Calgary soccer clubs (male or female, U13-U18, tier 1-2, indoor soccer). PARTICIPANTS: Eighty-two soccer teams were approached for recruitment. Players from 60 teams completed the study (32 training (n=380), 28 control (n=364)). INTERVENTION: The training programme was a soccer-specific neuromuscular training programme including dynamic stretching, eccentric strength, agility, jumping and balance (including a home-based balance training programme using a wobble board). The control programme was a standardised warm-up (static and dynamic stretching and aerobic components) and a home-based stretching programme. MAIN OUTCOME MEASURES: Previously validated injury surveillance included injury assessment by a study therapist. The injury definition was soccer injury resulting in medical attention and/or removal from a session and/or time loss. RESULTS: The injury rate in the training group was 2.08 injuries/1000 player-hours, and in the control group 3.35 injuries/1000 player-hours. Based on Poisson regression analysis, adjusted for clustering by team and covariates, the incidence rate ratios (IRR) for all injuries and acute onset injury were 0.62 (95% CI 0.39 to 0.99) and 0.57 (95% CI 0.35 to 0.91). Point estimates also suggest protection of lower extremity, ankle and knee sprain injuries (IRR=0.68 (95% CI 0.42 to 1.11), IRR=0.5 (95% CI 0.24 to 1.04) and IRR=0.38 (95% CI 0.08 to 1.75)). CONCLUSIONS: A neuromuscular training programme is protective of all injuries and acute onset injury in youth soccer players.