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Tibiofemoral compression forces present during locomotion can result in high stress and risk damage to the knee. Powered assistance using a knee exoskeleton may reduce the knee load by reducing the work required by the muscles. However, the exact effect of assistance on the tibiofemoral force is unknown. The goal of this study was to investigate the effect of knee extension assistance during the early stance phase on the tibiofemoral force. Nine able-bodied adults walked on an inclined treadmill with a bilateral knee exoskeleton with assistance and with no assistance. Using an EMG-informed neuromusculoskeletal model, muscle forces were estimated, then utilized to estimate the tibiofemoral contact force. Results showed a 28% reduction in the knee moment, which resulted in approximately a 15% decrease in knee extensor muscle activation and a 20% reduction in subsequent muscle force, leading to a significant 10% reduction in peak and 9% reduction in average tibiofemoral contact force during the early stance phase (p < 0.05). The results indicate the tibiofemoral force is highly dependent on the knee kinetics and quadricep muscle activation due to their influence on knee extensor muscle forces, the primary contributor to the knee load.