The knee is a complex joint that is difficult to model accurately. Although significant advances have been made in mathematical modeling, these have yet to be validated successfully in vivo. Direct measurement of knee forces should lead to a better understanding of the stresses seen in total knee arthroplasty. An instrumented knee prosthesis was developed to measure forces in vivo after total knee arthroplasty. An instrumented tibial prosthesis was implanted in an 80-year-old male weighing 66 kg. The prosthesis measured forces at the four corners of the tibial tray. The patient walked approximately 1.6million steps per year before surgery (ankle accelerometer measurements). Knee forces were measured postoperatively during passive and active knee flexion, rehabilitation, rising from a chair, standing, walking, and climbing stairs. The patient was walking with the help of a walker by postoperative day 3. Peak tibial forces were 1.2 times body weight (BW). By the sixth postoperative day the tibial forces during gait were 1.7 times BW. At six weeks the peak tibial forces during walking had risen to 2.4time BW. Stair climbing increased from 1.9 times BW on day 6 to 3.3 times BW at six weeks. This represents the first direct in vivo measurement of tibial forces. In vivo tibiofemoral force data will be used to develop better biomechanical knee models and in vitro wear tests and will be used to evaluate the effect of improvements in implant design and bearing surfaces, rehabilitation protocols, and orthotics. This should lead to refining surgical techniques and to enhancing prosthetic designs that will improve function, quality of life, and longevity of total knee arthroplasty. This information is vital given the current trend in the increase of older population groups that are at higher risk for chronic musculoskeletal disorders.