8 in 10 people with an amputation desire to participate in physical activity, yet lack of prosthetic availability and inadequately designed prostheses are the primary barriers for participation in sports and activities. Furthermore, the population of people with an amputation is predicted to more than double by the year 2050. Physical activity is beneficial for physical, social, and emotional health, and is important for maintaining a healthy lifestyle, especially for people who have had an amputation. Running-specific prostheses (RSPs) are designed for running and sprinting due to their large energy storage and return capabilities. However, RSPs are expensive and may not be covered by medical insurance. Therefore, if a person with an amputation wishes to run, they may do so using their daily-use prosthesis (DUP), which is not designed for highly dynamic activities. People with a unilateral transtibial amputation (TTA) have numerous biomechanical differences between the intact and amputated legs, and compared to people without TTA. TTA results in changes in joint kinetics, ground reaction forces, muscular coordination, and internal joint loading, which has been previously observed during walking. However, the effect of amputation together with the effect of prosthesis choice (DUP vs. RSP) and running speed have not been investigated among people with TTA during running. Characterizing the running biomechanics of people with TTA is important for understanding implications of device choice and amputation on outcomes related to overall functionality and long-term injury, which is prevalent for people with TTA. Therefore, the purpose of this work was to characterize the running biomechanics of people with TTA to understand the effect of prosthesis choice (RSP vs. DUP), the presence of an amputation, and running speed on coordination and injury risk. People with and without TTA ran at speeds ranging from 2.5 m/s to 5.0 m/s (10:​44 min/mile - 5:​21 min/mile) while kinematics, kinetics, and muscle activity were collected. Musculoskeletal models were developed to estimate internal hip joint contact forces. Compared to DUPs, the use of RSPs reduced the amount of compensatory amputated side hip work, increased device energy return, reduced total muscle activity, improved peak muscle activation timing, and reduced bilateral peak hip joint contact forces. Understanding the effects of amputation, prosthesis type, and running speed on metrics related to injury risk for people with TTA is important for informing device selection, providing evidence for medical insurance coverage, and improving long-term joint health outcomes. Outcomes from this research have the potential to improve device availability and ultimately, eliminate barriers for people with TTA to freely participate in running and sporting activities.