Ankle-foot orthoses (AFO) are commonly prescribed to provide functional assistance for patients with lower limb injuries or weakness. Their passive mechanical elements can provide some energy return to improve walking ability, but cannot restore plantar flexor push-off. Powered AFOs provide an assistive torque about the ankle to address the limitations of passive devices, but current designs have yet to be implemented on a large scale clinically. To compare passive AFOs to a new untethered, powered AFO design in a clinical population with lower limb reconstruction. A crossover study design, conducted on three individuals with lower limb reconstruction, compared gait mechanics at a standardized speed (based on leg length) in 4 AFO conditions: 1. None (shoes only), 2. Blue Rocker (BR, Allard, USA), 3. Intrepid Dynamic Exoskeletal Orthosis (IDEO), and 4. PowerFoot Orthosis (PFO BionX Medical Technologies, Inc.). The PFO was a custom, battery-powered device whose damping and power were capable to being tuned to meet patient needs. Subjects performed biomechanical gait analysis and metabolic testing at slow, moderate and fast speeds. Dependent variables included total limb power (calculated using a unified deformable segment model), mechanical work, mechanical efficiency, ankle motion, net metabolic cost across three speeds, and performance measures were calculated. Effect sizes (d) were calculated and d > 0.80 denoted a large effect. Net positive work (d > 1.17) and efficiency (d > 1.43) were greatest in the PFO. There were large effects for between limb differences in positive work for all conditions except the PFO (d = 0.75). The PFO normalized efficiency between the affected and unaffected limbs (d = 0.50), whereas efficiency was less on the affected limb for all other conditions (d > 1.69). Metabolic rate was not consistently lowest in any one AFO condition across speeds. Despite some positive results of the PFO, patient preferred their daily use AFO (2 IDEO, 1 BR). All participants indicated that mass and size were concerns with using the PFO. A novel PFO resulted in more biomimetic mechanical work and efficiency than commercially-available and custom passive AFO models. Although the powered AFO provided some biomechanical benefits, further improvements are warranted to improve patient satisfaction.