Unilateral below-knee amputees commonly experience asymmetrical gait patterns and develop comorbidities in their intact (non-amputated) and residual (amputated) legs, with the mechanisms leading to these asymmetries and comorbidities being poorly understood. Prosthetic feet have been designed in an attempt to minimize walking asymmetries by utilizing elastic energy storage and return (ESAR) to help provide body support, forward propulsion and leg swing initiation. However, identifying the influence of walking speed and prosthetic foot stiffness on amputee gait mechanics is needed to develop evidence-based rationale for prosthetic foot selection and treatment of comorbidities. In this research, experimental and modeling studies were performed to identify the influence of walking speed and prosthetic foot stiffness on amputee walking mechanics. The results showed that when asymptomatic and relatively new amputees walk using clinically prescribed prosthetic feet across a wide range of speeds, loading asymmetries exist between the intact and residual knees. However, knee intersegmental joint force and moment quantities in both legs were not higher compared to non-amputees, suggesting that increased knee loads leading to joint disorders may develop in response to prolonged prosthesis usage or the onset of joint pathology over time. In addition, the results showed that decreasing ESAR foot stiffness can increase prosthesis range of motion, mid-stance energy storage, and late-stance energy return. However, the prosthetic foot contributions to forward propulsion and swing initiation were limited due to muscle compensations needed to provide body support and forward propulsion in the absence of residual leg ankle muscles. A study was also performed that integrated design optimization with forward dynamics simulations of amputee walking to identify the optimal prosthetic foot stiffness that minimized metabolic cost and intact knee joint forces. The optimal stiffness profile stiffened the toe and mid-foot while making the ankle less stiff, which decreased the intact knee joint force during mid-stance while reducing the overall metabolic cost of walking. These studies have provided new insight into the relationships between prosthetic foot stiffness and amputee walking mechanics, which provides biomechanics-based rationale for prosthetic foot prescription that can lead to improved amputee mobility and overall quality of life. / text