Musculo-skeletal loading plays an important role in the primary stability of joint replacements and in the biological processes involved in fracture healing. However, current knowledge of musculo-skeletal loading is still limited. In the past, a number of musculo-skeletal models have been developed to estimate loading conditions at the hip. So far, a cycle-to-cycle validation of predicted musculo-skeletal loading by in vivo measurements has not been possible. The aim of this study was to determine the musculo-skeletal loading conditions during walking and climbing stairs for a number of patients and compare these findings to in vivo data. Following total hip arthroplasty, four patients underwent gait analysis during walking and stair climbing. An instrumented femoral prosthesis enabled simultaneous measurement of in vivo hip contact forces. On the basis of CT and X-ray data, individual musculo-skeletal models of the lower extremity were developed for each patient. Muscle and joint contact forces were calculated using an optimization algorithm. The calculated peak hip contact forces both over- and under-estimated the measured forces. They differed by a mean of 12% during walking and 14% during stair climbing. For the first time, a cycle-to-cycle validation of predicted musculo-skeletal loading was possible for walking and climbing stairs in several patients. In all cases, the comparison of in vivo measured and calculated hip contact forces showed good agreement.Thus, the authors consider the presented approach as a useful means to determine valid conditions for the analysis of prosthesis loading, bone modeling or remodeling processes around implants and fracture stability following internal fixation.