Many field sports involve equipment that restricts one or both arms from moving while running. Arm swing during running has been examined from a biomechanical and physiologic perspective but not from an injury perspective. Moreover, only bilateral arm swing suppression has been studied with respect to running. The purpose of this study was to determine the influence of running with one arm restrained on lower extremity mechanics associated with running or sport-related injury. Fifteen healthy participants ran at a self-selected speed with typical arm swing, with one arm restrained and with both arms restrained. Lower extremity kinematics and spatiotemporal measures were analysed for all arm swing conditions. Running with one arm restrained resulted in increased frontal plane knee and hip angles, decreased foot strike angle, and decreased centre of mass vertical displacement compared to typical arm swing or bilateral arm swing restriction. Stride length was decreased and step frequency increased when running with one or both arms restrained. Unilateral arm swing restriction induces changes in lower extremity kinematics that are not similar to running with bilateral arm swing restriction or typical arm swing motion. Running with one arm restrained increases frontal plane mechanics associated with risk of knee injury.