Background:Female athletes have a higher rate of anterior cruciate ligament (ACL) injury than males from adolescence and into maturity, which is suggested to result from sex-specific changes in dynamic movement patterns with maturation. Few studies have studied movement strategies and response to fatigue in children.Purpose:To evaluate the effect of fatigue on biomechanical variables associated with increased risk for ACL injury during a drop-jump (DJ) performance in children.Study Design:Controlled laboratory study.Methods:A total of 116 children (mean age, 10.4 years) were recruited from local sports clubs and performed 5 repetitions of a DJ task before and after a fatigue protocol. Kinematic and kinetic data from initial contact (IC) to the first peak vertical ground reaction force (vGRF) were analyzed for both limbs, including limb and fatigue as within-subject factors for analyses between boys and girls. Pearson correlation coefficients were calculated to identify associations between variables of interest.Results:Girls demonstrated greater peak vGRF values than boys (by 8.1%; P < .05), there were greater peak vGRF values for the right limb than the left (by 6.2%; P < .001), and fatigue led to slightly greater values (P < .05). Although weak, the correlation between peak vGRF values and knee flexion excursion was stronger for girls (r = –0.20) than boys (r = –0.08) (P < .006). Fatigue resulted in greater knee flexion angles at IC and less excursion during landing, more so for girls (by 6.1° vs 1.4°; interaction, P < .001), although the knee flexion moment was generally lowered by fatigue (P < .001). Limb asymmetry in knee flexion moments was more pronounced for boys than for girls (interaction, P < .05), contrary to that seen in frontal plane knee moments, where asymmetry was much greater in girls than boys (interaction, P < .001).Conclusion:Even as young athletes, girls and boys seem to adopt dissimilar movement strategies and are differently affected by fatigue.Clinical Relevance:Injury prevention programs should be considered at an earlier age in an effort to lower the risk of ACL injury in athletes.