Lower　extremity　musculoskeletal　computational　models　play　an　important　role　in　predicting　joint　forces　and　muscle　activation　simultaneously　and　are　valuable　for　investigating　functional　outcomes　of　the　implants.　However,　current　computational　musculoskeletal　models　of　total　knee　replacement　rarely　consider　the　bearing　surface　geometry　of　the　implant.　Therefore,　these　models　lack　detailed　information　about　the　contact　loading　and　joint　motion　which　are　important　factors　for　evaluating　clinical　performances.　This　study　extended　a　rigid　multi-body　dynamics　simulation　of　a　lower　extremity　musculoskeletal　model　to　incorporate　an　artificial　knee　joint,　based　upon　a　novel　force-dependent　kinematics　method,　and　to　characterize　the　in　vivo　joint　contact　mechanics　during　gait.　The　developed　musculoskeletal　total　knee　replacement　model　integrated　the　rigid　skeleton　multi-body　dynamics　and　the　flexible　contact　mechanics　of　the　tibiofemoral　and　patellofemoral　joints.　The　predicted　contact　forces　and　muscle　activations　are　compared　against　those　in　vivo　measurements　obtained　from　a　single　patient　with　good　agreements　for　the　medial　contact　force　(root-mean-square　error　=　215　N,　ρ　=　0.96)　and　lateral　contact　force　(root-mean-square　error　=　179　N,　ρ　=　0.75).　Moreover,　the　developed　model　also　predicted　the　motion　of　the　tibiofemoral　joint　in　all　degrees　of　freedom.　This　new　model　provides　an　important　step　toward　the　development　of　a　realistic　dynamic　musculoskeletal　total　knee　replacement　model　to　predict　in　vivo　knee　joint　motion　and　loading　simultaneously.　This　could　offer　a　better　opportunity　to　establish　a　robust　virtual　modeling　platform　for　future　pre-clinical　assessment　of　knee　prosthesis　designs,　surgical　procedures　and　post-operation　rehabilitation.