Background/Objectives: Lower-limb amputation significantly impacts autonomy and daily functioning. Microprocessor-controlled prosthetic knees (MPKs) improve mobility, safety, and quality of life compared with non-microprocessor prosthetic knees (nMPKs). Despite general benefits, differences among MPK models remain unclear. The goal of this investigation was to evaluate functional mobility and patient-reported outcomes in active transfemoral amputees using a new MPK (PROTEOR QUATTRO) compared with existing MPKs. Methods: In this multicenter cross-over clinical trial, active transfemoral amputees were assessed using patient-specific functional scales (PSFS), standardized locomotor capacity tests (6MWT, 10mWT, HAI, SAI) and satisfaction and quality-of-life questionnaires (PEQ-A, SF-36, ESAT). Biomechanical data collection was performed during walking test, to examine gait symmetry indices. Results: The QUATTRO MPK was associated with significantly higher PSFS scores, reflecting higher self-rated ability in performing chosen daily life activities compared with patient’s current prosthesis. Standardized locomotor tests revealed comparable performance between devices. Biomechanical analyses showed similar symmetry indices for QUATTRO and other MPKs. Patient-reported outcomes showed an improvement in physical health with QUATTRO, while overall satisfaction remained similar. Conclusions: QUATTRO improved patient-perceived ability to perform meaningful daily-life activities while maintaining comparable performance on standardized locomotor tests. These results highlight the importance of patient-centered assessments in identifying functional benefits that may guide individualized prosthetic prescriptions for active transfemoral amputees.