Background <p>Commercially-available microprocessor-controlled prosthetic knees are unable to fully replicate the biomechanical function of the missing biological limb. While powered prostheses have the capacity to restore joint level kinetics, current systems rely on intrinsic control schemes that do not allow the user to volitionally modulate movement under neural commands. This limitation may compromise functional performance and hinder prosthetic embodiment, the sense that the device is part of the user’s body. In a case study on one test participant, we evaluate the functional and perceptual benefits of a bone-anchored, neurally-controlled knee prosthesis by comparing it to the participant’s microprocessor-controlled prosthesis.</p> Methods <p>We conducted a within-subject study on an individual with a transfemoral amputation, with an osseointegrated implant and surgically reconstructed agonist–antagonist muscle pairs. We tested a neurally-controlled powered knee and conventional microprocessor knee across a set of activities, including seated volitional control tasks, sit-to-stand transitions, squatting, level-ground walking, stair ascent, and uninstructed standing. Performance metrics included knee kinematics, prosthesis-generated mechanical power, and functional outcomes such as gait speed, stair ascent time, and weight-bearing symmetry derived from ground reaction forces. Functional mobility and control were complemented by self-reported embodiment, assessed through a questionnaire targeting agency, ownership, and body representation.</p> Results <p>The neurally-controlled prosthesis enabled intuitive and responsive control. Compared to the subject’s prescribed prosthesis, the prosthesis yielded improved temporal gait symmetry during walking (symmetry index: 0.93 vs. 0.59, with 1 indicating perfect stance time symmetry), increased prosthetic-side weight-bearing during sit-to-stand and squatting, and successful execution of a step-over-step stair ascent strategy—an outcome not achievable with the subject’s prescribed device. Embodiment scores were consistently higher with the neurally-controlled prosthesis compared to the prescribed device across multiple domains, including agency, ownership and body representation.</p> Conclusions <p>This study is the first to directly compare a prescribed microprocessor knee with a bone-anchored, neurally-controlled powered prosthesis. By combining osseointegration, surgically reconstructed agonist–antagonist muscle pairs, and powered actuation, the system improved gait symmetry, greater prosthetic-side loading, and step-over-step stair ascent. These results demonstrate the novelty and promise of integrating surgical and mechatronic innovations to restore both functional mobility and embodied control after transfemoral amputation.</p> <i>Trial registration</i> <p>This study was approved by the Institutional Review Board at MIT (Protocol No. 2503001589).</p>