The main objective of this study is to develop a computational human musculoskeletal model, used to investigate the change in the kinematic behavior of the model’s lower extremities under the influence of activated (active) and deactivated (passive) muscles, during a representative frontal collision using the OpenSim software. Since OpenSim is seldom used in crash simulations, an appropriate model evaluation is performed by comparing the model’s kinematics, obtained from the OpenSim’s inverse dynamic simulation, against the LS-DYNA’s explicit non-linear side impact simulation of a finite element model for a car-pedestrian collision. The required musculoskeletal model is constructed in OpenSim and scaled to meet the requirements of the Hybrid III 50th percentile crash test dummy. For evaluating the developed model, the kinematics from both programs (OpenSim and LS-DYNA), containing identical displacement data, are compared by visual observation of identical time frames. Using the evaluated model in the forward dynamics domain of OpenSim, representative frontal crash simulations are conducted for the active and passive muscle states of the musculoskeletal model, and the kinematic differences in the human model’s lower extremities are extracted and compared.