Alterations of foot rotation angles have successfully reduced external knee abduction moments during walking and running. However, reductions in knee abduction loads may not result in reductions in knee joint reaction forces. The purpose of this study was to examine the effects of internal and external foot rotation on knee, hip, and ankle joint reaction forces during running. Motion capture and force data were recorded of nineteen healthy adults running at 3.5 m/s during three conditions: 1) normal, and maximal comfortable 2) internal and 3) external foot rotation. Musculoskeletal simulations were performed using OpenSim and the Rajagopal 2015 model, modified to a two degree of freedom knee joint. Muscle excitations were derived using static optimization, including muscle physiology parameters. Joint reaction forces were obtained by combining inverse kinematics, force data, and muscle excitations. Differences between joint reaction force waveforms were determined using one-way ANOVAs via statistical parametric mapping. Internal and external foot rotation reduced resultant hip and ankle forces throughout the stance phase. Three-dimensional and resultant Knee joint reaction forces only differed at very early and very late stance phase. The results of this study indicate, similar to previous findings, that reductions in external knee abduction moments do not mirror reductions in knee joint reaction forces.