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Approximately two-thirds of anterior cruciate ligament (ACL) tears are sustained during noncontact situations when an athlete is cutting, pivoting, decelerating, or landing from a jump. Some investigators have postulated that fatigue may result in deleterious alterations in lower limb biomechanics during these activities that could increase the risk of noncontact ACL injuries. However, prior studies have noted a wide variation in fatigue protocols, athletic tasks studied, and effects of fatigue on lower limb kinetics and kinematics.First, to determine if fatigue uniformly alters lower limb biomechanics during athletic tasks that are associated with noncontact ACL injuries. Second, to determine if changes should be made in ACL injury prevention training programs to alter the deleterious effects of fatigue on lower limb kinetics and kinematics.Systematic review; Level of evidence, 4.A systematic review of the literature using MEDLINE was performed. Key terms were fatigue, neuromuscular, exercise, hop test, and single-legged function tests. Inclusion criteria were original research studies involving healthy participants, use of a fatigue protocol, study of at least 1 lower limb task that involved landing from a hop or jump or cutting, and analysis of at least 1 biomechanical variable.Thirty-seven studies involving 806 athletes (485 female, 321 male; mean age, 22.7 years) met the inclusion criteria. General fatigue protocols were used in 20 investigations, peripheral protocols were used in 17 studies, and 21 different athletic tasks were studied (13 single-legged, 8 double-legged). There was no consistency among investigations regarding the effects of fatigue on hip, knee, or ankle joint angles and moments or surface electromyography muscle activation patterns. The fatigue protocols typically did not produce statistically significant changes in ground-reaction forces.Published fatigue protocols did not uniformly produce alterations in lower limb neuromuscular factors that heighten the risk of noncontact ACL injuries. Therefore, justification does not currently exist for major changes in ACL injury prevention training programs to account for potential fatigue effects. However, the effect of fatigue related to ACL injuries is worthy of further investigation, including the refinement of protocols and methods of analysis.