People with a lower-extremity amputation that use conventional passive-elastic ankle-foot prostheses encounter a series of stress-related challenges during walking such as greater forces on their unaffected leg, and may thus be predisposed to secondary musculoskeletal injuries such as chronic joint disorders. Specifically, people with a unilateral transtibial amputation have an increased susceptibility to knee osteoarthritis, especially in their unaffected leg. Previous studies have hypothesized that the development of this disorder is linked to the abnormally high peak knee external adduction moments encountered during walking. An ankle-foot prosthesis that supplies biomimetic power could potentially mitigate the forces and knee adduction moments applied to the unaffected leg of a person with a transtibial amputation, which could, in turn, reduce the risk of knee osteoarthritis. We hypothesized that compared to using a passive-elastic prosthesis, people with a transtibial amputation using a powered ankle-foot prosthesis would have lower peak resultant ground reaction forces, peak external knee adduction moments, and corresponding loading rates applied to their unaffected leg during walking over a wide range of speeds. We analyzed ground reaction forces and knee joint kinetics of the unaffected leg of seven participants with a unilateral transtibial amputation and seven age-, height- and weight-matched non-amputees during level-ground walking at 0.75, 1.00, 1.25, 1.50, and 1.75 m/s. Subjects with an amputation walked while using their own passive-elastic prosthesis and a powered ankle-foot prosthesis capable of providing net positive mechanical work and powered ankle plantar flexion during late stance. Use of the powered prosthesis significantly decreased unaffected leg peak resultant forces by 2-11% at 0.75-1.50 m/s, and first peak knee external adduction moments by 21 and 12% at 1.50 and 1.75 m/s, respectively. Loading rates were not significantly different between prosthetic feet. Use of a biomimetic powered ankle-foot prosthesis decreased peak resultant force at slow and moderate speeds and knee external adduction moment at moderate and fast speeds on the unaffected leg of people with a transtibial amputation during level-ground walking. Thus, use of an ankle-foot prosthesis that provides net positive mechanical work could reduce the risk of comorbidities such as knee osteoarthritis.