The purpose of this study was to develop a subject-specific 3-D model of the lower extremity to predict neuromuscular control effects on 3-D knee joint loading during movements that can potentially cause injury to the anterior cruciate ligament (ACL) in the knee. The simulation consisted of a forward dynamic 3-D musculoskeletal model of the lower extremity, scaled to represent a specific subject. Inputs of the model were the initial position and velocity of the skeletal elements, and the muscle stimulation patterns. Outputs of the model were movement and ground reaction forces, as well as resultant 3-D forces and moments acting across the knee joint. An optimization method was established to find muscle stimulation patterns that best reproduced the subject’s movement and ground reaction forces during a sidestepping task. The optimized model produced movements and forces that were generally within one standard deviation of the measured subject data. Resultant knee joint loading variables extracted from the optimized model were comparable to those reported in the literature. The ability of the model to successfully predict the subject’s response to altered initial conditions was quantified and found acceptable for use of the model to investigate the effect of altered neuromuscular control on knee joint loading during sidestepping. Monte Carlo simulations (N=100,000) using randomly perturbed initial kinematic conditions, based on the subject’s variability, resulted in peak anterior force, valgus torque and internal torque values of 378 N, 94 Nm and 71 Nm, respectively, large enough to cause ACL rupture. We conclude that the procedures described in this paper were successful in creating valid simulations of normal movement, and in simulating injuries that are caused by perturbed neuromuscular control.