Objective To establish a personalized musculoskeletal multi-body dynamics model of total knee replacement (TKR) by two software nmsBuilder and OpenSim, and verify this established model by using bouncy and medthrust gait patterns. Methods Based on skeletal data from a patient, the body, skeletal landmark clouds and muscular landmark clouds were established for automatically generating reference systems and muscles. The musculoskeletal model generated by nmsBuilder was introduced into OpenSim, and inverse kinematics, static optimization and knee joint force analysis were performed successively. Finally, the model was driven by bouncy gait and medthrust gait respectively, and the results were compared with experimental measurements. Results Except for the lateral joint contact forces, the predicted magnitude and trend of knee joint contact forces by the model had a good agreement with the experimental data, and the constructed skeletal muscle multi-body dynamics model could be used for knee joint research. Conclusions The established musculoskeletal multi-body dynamics model could predict the medial, lateral and total tibiofemoral joint contact forces simultaneously by inputting the marker positions and the ground reaction forces. The research ideas of this study can provide references for designing personalized knee prostheses for TKR patient.