While the increased incidence of serious knee injuries in female athletes is well established, the underlying neuromuscular mechanisms related to the elevated ACL injury rate has yet to be delineated. Video analysis of ACL injury during competitive sports play indicates a common body position associated with non-contact ACL injury; the tibia is externally rotated, the knee is close to full extension, the foot is planted and as the limb is decelerated it collapses into valgus. The purpose of the current prospective study was to evaluate gender differences in quadriceps muscle activation strategies when performing a physically challenging, but reproducible maneuver that mimics the high ACL injury risk position (in the absence of high velocity and high loads). Twenty physically active college-aged subjects (10 male and 10 female) performed multiple sets of the prescribed exercise. EMG recordings were employed to measure the ratio of activation between the medial and lateral quadriceps during the 4, 8, 12, 16, and 20th sets of exercise. Females demonstrated decreased RMS medial-to-lateral quadriceps ratios compared to males (F(1,18)=5.88, p=0.026). There was no main effect of set number on RMS quadriceps ratio (p>0.05). The results of this study suggest that females utilize neuromuscular activation strategies which may contribute to "dynamic valgus" and ACL rupture when performing high-risk maneuvers.