OBJECTIVE: To examine the effect of a comprehensive warm-up programme designed to reduce the risk of injuries in female youth football. DESIGN: Cluster randomised controlled trial with clubs as the unit of randomisation. SETTING: 125 football clubs from the south, east, and middle of Norway (65 clusters in the intervention group; 60 in the control group) followed for one league season (eight months). PARTICIPANTS: 1892 female players aged 13-17 (1055 players in the intervention group; 837 players in the control group). INTERVENTION: A comprehensive warm-up programme to improve strength, awareness, and neuromuscular control during static and dynamic movements. MAIN OUTCOME MEASURE: Injuries to the lower extremity (foot, ankle, lower leg, knee, thigh, groin, and hip). RESULTS: During one season, 264 players had relevant injuries: 121 players in the intervention group and 143 in the control group (rate ratio 0.71, 95% confidence interval 0.49 to 1.03). In the intervention group there was a significantly lower risk of injuries overall (0.68, 0.48 to 0.98), overuse injuries (0.47, 0.26 to 0.85), and severe injuries (0.55, 0.36 to 0.83). CONCLUSION: Though the primary outcome of reduction in lower extremity injury did not reach significance, the risk of severe injuries, overuse injuries, and injuries overall was reduced. This indicates that a structured warm-up programme can prevent injuries in young female football players. TRIAL REGISTRATION: ISRCTN10306290.