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Background: The above-knee amputation of a lower limb is a severe impairment that affects significantly the ability to walk; considering this, a complex adaptation strategy at the neuromuscular level is needed in order to be able to move safely with a prosthetic knee. In literature, it has been demonstrated that muscle activity during walking can be described via the activation of a small set of muscle synergies. The analysis of the composition and the time activation profiles of such synergies have been found to be a valid tool for the description of the motor control schemes in pathological subjects., Methods: In this study, we used muscle synergy analysis techniques to characterize the differences in the modular motor control schemes between a population of 14 people with trans-femoral amputation and 12 healthy subjects walking at two different (slow and normal self-selected) speeds. Muscle synergies were extracted from a 12 lower-limb muscles sEMG recording via non-negative matrix factorization. Equivalence of the synergy vectors was quantified by a cross-validation procedure, while differences in terms of time activation coefficients were evaluated through the analysis of the activity in the different gait sub-phases., Results: Four synergies were able to reconstruct the muscle activity in all subjects. The spatial component of the synergy vectors did not change in all the analysed populations, while differences were present in the activity during the sound limb's stance phase. Main features of people with trans-femoral amputation's muscle synergy recruitment are a prolonged activation of the module composed of calf muscles and an additional activity of the hamstrings' module before and after the prosthetic heel strike., Conclusions: Synergy-based results highlight how, although the complexity and the spatial organization of motor control schemes are the same found in healthy subjects, substantial differences are present in the synergies' recruitment of people with trans femoral amputation. In particular, the most critical task during the gait cycle is the weight transfer from the sound limb to the prosthetic one. Future studies will integrate these results with the dynamics of movement, aiming to a complete neuro-mechanical characterization of people with trans-femoral amputation's walking strategies that can be used to improve the rehabilitation therapies.