Our current knowledge of individuals with lower extremity amputation (ILEA) running is limited with respect to biomechanical performance and injury risks. ILEA are able to run with both running specific prostheses (RSPs) and traditional prostheses (TPs); however, direct comparisons of subjects running with each of these prosthetic designs do not exist. Furthermore, no ILEA running studies to date have investigated muscle activities, nor have running simulations of musculoskeletal models been generated. These major gaps in research substantially limit our understanding of both performance and injury risk of ILEA running with different prosthetic designs. Gaining this knowledge will directly inform clinicians on prosthesis prescription for running at a range of speeds as well as for return to duty scenarios. Therefore, the purpose of this study is to utilize motion capture, muscle activity, and musculoskeletal modeling techniques to directly compare performance and injury risks of ILEA running with both RSPs and TPs across a range of speeds.