Purpose The goal was to evaluate the effect of total ankle replacement (TAR) on gait in terms of mechanical and energetic variables. Methods An observational, prospective study was undertaken in 20 patients before and approximately 7 months after unilateral mobile-bearing TAR. The clinical–functional level was assessed according to the American Orthopaedic Foot and Ankle Society ‘AOFAS’. An instrumented motion analysis was used to assess spatiotemporal parameters, ankle kinematics, mechanical work, and electromyographic activity. Energy expenditure was analyzed using an ergospirometer. Results AOFAS score improved 1.5 times. The speed was also significantly improved. In order to limit the influence of speed and to highlight the effect of the surgery, all variables were normalized by z-score to isolate the effect of TAR. With normalized z-score, spatiotemporal parameters and ankle amplitude instance were significantly improved. The vertical center of mass displacement was significantly improved, showing a less flat-walking pattern, and decreasing energy expenditure. Our results show that TAR has a beneficial effect on locomotor function. Conclusions Many studies have shown that improved clinical outcomes can be expected with the new generation of prostheses and this was as confirmed by our study. However, no previous study has investigated the effect of TAR on the functional limitations of gait as represented by mechanical and energetic variables.