This paper presents the mechanical design, control scheme, and clinical evaluation of a novel, motorized ankle-foot prosthesis, called MIT Powered Ankle-Foot Prosthesis. Unlike a conventional passive-elastic ankle-foot prosthesis, this prosthesis can provide active mechanical power during the stance period of walking. The basic architecture of the prosthesis is a unidirectional spring, configured in parallel with a force-controllable actuator with series elasticity. With this architecture, the anklefoot prosthesis matches the size and weight of the human ankle, and is also capable of delivering high mechanical power and torque observed in normal human walking. We also propose a biomimetic control scheme that allows the prosthesis to mimic the normal human ankle behavior during walking. To evaluate the performance of the prosthesis, we measured the rate of oxygen consumption of three unilateral transtibial amputees walking at self-selected speeds to estimate the metabolic walking economy. We find that the powered prosthesis improves amputee metabolic economy from 7% to 20% compared to the conventional passive-elastic prostheses (Flex-Foot Ceterus and Freedom Innovations Sierra), even though the powered system is twofold heavier than the conventional devices. This result highlights the benefit of performing net positive work at the ankle joint to amputee ambulation and also suggests a new direction for further advancement of an ankle-foot prosthesis.