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A generic finite element (FE) model of the lower limb was used to study the knee response in-vivo during a one-legged hop. The approach uses an explicit FE code and a combination of estimated muscle forces and measured three-dimensional tibio-femoral kinematics and ground reaction force as input to the FE model. The sensitivity of the simulated tibio-femoral response to variations of key geometric and material parameters was investigated by performing a total of 38 different simulations. The amplitudes of both kinematic and kinetic responses were affected by the change of these parameters. For the current approach, the results suggest that while cartilage mechanical and geometric properties are very important for the estimation of tibio-femoral cartilage pressure, they have limited effects on the overall kinematic response. The study may help to better define the relative importance of modeling parameters for the development of subject-specific models.