Knowledge of the behavior and mechanics of a total knee replacement (TKR) in an in vivo environment is key to optimizing the functional outcomes of the implant procedure. Computational modeling has shown to be an important tool for investigating biomechanical variables that are difficult to address experimentally. To assist in examining TKR mechanics, a dynamic finite-element model of a TKR is presented. The objective of the study was to develop and evaluate a model that could simulate full knee motion using a physiologically consistent quadriceps action, without prescribed joint kinematics. The model included tibiofemoral (TFJs) and patellofemoral joints (PFJs), six major ligament bundles and was driven by a uni-axial representation of a quadricep muscle. An initial parameter screening analysis was performed to assess the relative importance of 31 different model parameters. This analysis showed that ligament insertion location and initial ligament strain were significant factors affecting simulated joint kinematics and loading, with the contact friction coefficient playing a lesser role and ligament stiffness having little effect. The model was then used to simulate in vitro experiments utilizing a flexed-knee-stance testing rig. General model performance was assessed by comparing simulation results with experimentally measured kinematics and tibial reaction forces collected from two implanted specimens. The simulations were able to reproduce experimental differences observed between the test specimens and were able to accurately predict trends seen in the tibial reaction loads. The simulated kinematics of the TFJ and PFJ were less consistent when compared with experimental data but still reproduced many trends.