This article evaluates the design of a variable impedance prosthetic (VIPr) socket for a transtibial amputee using computer-aided design and manufacturing (CAD/CAM) processes. Compliant features are seamlessly integrated into a three-dimensional printed socket to achieve lower interface peak pressures over bony protuberances by using biomechanical data acquired through surface scanning and magnetic resonance imaging techniques. An inverse linear mathematical transformation spatially maps quantitative measurements (bone tissue depth) of the human residual limb to the corresponding prosthetic socket impedance characteristics. The CAD/CAM VIPr socket is compared with a state-of-the-art prosthetic socket of similar internal geometry and shape designed by a prosthetist using conventional methods. An active bilateral transtibial male amputee of weight 70 kg walked on a force plate–embedded 5-m walkway at self-selected speeds while synchronized ground reaction forces, motion capture data, and socket-residual limb interface pressures were measured for the evaluated sockets. Contact interface pressure recorded (using Teksan F-Socket™ pressure sensors) during the stance phase of several completed gait cycles indicated a 15% and 17% reduction at toe-off and heelstrike, respectively, at the fibula head region while the subject used a VIPr socket in comparison with a conventional socket of similar internal shape. A corresponding 7% and 8% reduction in pressure was observed along the tibia. Similar trends of high-pressure reductions were observed during quiet single-leg standing with the VIPr socket in comparison with the conventional socket. These results underscore the possible benefits of spatially varying socket wall impedance based upon the soft tissue characteristics of the underlying residual limb anatomy.