Purpose/Hypotheses: The knee is the most commonly injured major joint, with approximately 80,000 anterior cruciate ligament (ACL) injuries annually. Epidemiological studies of sporting events show that knee injury frequency increases during during the latter portion of the game, thus injury may be associated with biomechanical changes induced by fatigue. We investigated the bilateral effects of unilateral lower extremity (LE) extensor muscle fatigue on electromyographic (EMG) patterns, kinematics, and kinetics of the single-leg vertical jump. Subjects: 15 healthy males, 22-29 years old. Methods: Subjects performed 5 maximal single-leg vertical jumps with each leg. Bilateral EMG (gluteus medius, vastus medialis and lateralis, medial and lateral hamstrings, gastroc/soleus), 3D lower extremity motion and ground reaction forces (GRF) from the jumping/landing leg were collected simultaneously. Subjects exercised the dominant LE (plant leg when kicking a ball) on a leg press machine to fatigue (unable to perform a complete leg press against resistance of 30% of body weight), then single-leg vertical jumps were repeated. Data were exracted in relation to landing events – initial force plate contact and the peak vertical GRF. EMG data were averaged across 5 trials and normalized as a percentage of the pre-exercise value for each muscle. Data analysis used repeated measures ANOVA and MANOVA. Results: There were significant interactions between limb dominance and fatigue for frontal plane knee valgus/varus moment (p=.035; larger on the dominant knee after exercise) and peak vertical GRF (p=.013; lower on the dominant leg after exercise). There was also a main effect of fatigue on peak anterior shear ground reaction force (p=.008; greater for the dominant leg after exercise). The dominant leg had significantly greater EMG activity of the gluteus medius and medial hamstring muscle groups. Conclusion: Despite reduced vertical and anterior GRF following exercise, landing from a single-leg vertical jump produced greater knee valgus moments and more EMG activity in the gluteus medius ad medial hamstring muscle groups in the dominant (exercised) leg and greater lateral hamstring and gastroc/soleus EMG activity in the non-dominant leg. Clinical Relevance: The change in post-fatigue forces in the dominant limb, particularly increased knee valgus moments, may increase the risk of ACL injury. The post-fatigue increase in gluteus medius and medial hamstring activity may be compensatory strategies to counteract the potentially damaging forces.