<p>Transfemoral amputees face the need for prosthetic devices following amputation surgery, including the socket, pylon, and foot. Modern socket designs often incorporate an intervening liner to assist with cushioning needs. Such liners have a crucial role in terms of patient safety and comfort. This study investigates the impact of different prosthetic liner materials on relative stresses at the stump–prosthesis interface in transfemoral amputations by finite element analysis. Using a computational model of a virtual patient, the work probes the biomechanical behavior under dynamic loads associated with normal walking, climbing up stairs, and down stairs. Specifically, memory-foam, flexible polyurethane foam, and gel type liners were evaluated based on their material properties. Variations in vertical displacement, contact pressure, and longitudinal shear stress were quantified across the different activities for each liner type. Results suggested that the polyurethane foam material performed the best at minimizing stresses and providing comfort across activities, making the flexible polyurethane foam the most promising liner material tested. The findings emphasize the critical role of selecting the right materials in prosthetic limb development to better design prosthetic solutions to provide comfort and good performance for transfemoral amputees.</p>