Contractile activity (e.g. exercise) evokes numerous metabolic adaptations in human skeletal muscle including enhanced insulin action and substrate oxidation. However, there is inter-subject variation in the physiological responses to exercise, which may be linked with factors such as the degree of obesity. Roux-en-Y gastric bypass (RYGB) surgery reduces body mass in severely obese (BMI > 40 kg/m²) individuals; however, it is uncertain whether RYGB can potentiate responses to contractile activity in this potentially exercise-resistant population. To examine possible interactions between RYGB and contractile activity, muscle biopsies were obtained from severely obese patients before and after RYGB, differentiated into myotubes, and electrically stimulated, after which changes in insulin action and glucose oxidation were determined. Prior to RYGB, myotubes were unresponsive to electrical stimulation as indicated by no changes in insulin-stimulated glycogen synthesis and basal glucose oxidation. However, myotubes from the same patients at 1 month after RYGB increased insulin-stimulated glycogen synthesis and basal glucose oxidation when subjected to contraction. While unresponsive before surgery, contraction improved insulin-stimulated phosphorylation of AS160 (Thr642, Ser704) after RYGB. These data suggest that RYGB surgery may enhance the ability of skeletal muscle from severely obese individuals to respond to contractile activity.