Muscles induce large forces in the tibiofemoral joint during walking and thereby influence the health of tissues like articular cartilage and menisci. It is possible to walk with a wide variety of muscle coordination patterns, but the effect of varied muscle coordination on tibiofemoral contact forces remains unclear. The goal of this study was to determine the effect of varied muscle coordination on tibiofemoral contact forces. We developed a musculoskeletal model of a subject walking with an instrumented knee implant. Using an optimization framework, we calculated the tibiofemoral forces resulting from muscle coordination that reproduced the subject''s walking dynamics. We performed a large set of optimizations in which we systematically varied the coordination of muscles to determine the influence on tibiofemoral force. Model-predicted tibiofemoral forces arising with minimum muscle activation matched in vivo forces measured during early stance, but were greater than in vivo forces during late stance. Peak tibiofemoral forces during late stance could be reduced by increasing the activation of the gluteus medius, uniarticular hip flexors, and soleus, and by decreasing the activation of the gastrocnemius and rectus femoris. These results suggest that retraining of muscle coordination could substantially reduce tibiofemoral forces during late stance. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:769-776, 2014.