Background: Reverse total shoulder arthroplasty (RSA) increases deltoid muscle fiber recruitment and tension to compensate for deficient rotator cuff activity; however, it is unclear whether the anterior or middle deltoid becomes dominant and how the muscle activation profile changes postoperatively. Using minimally invasive electromyography, this study evaluated the activity of the deltoid and surrounding muscles during shoulder motion to assess muscle activation changes post-RSA. Methods: In this observational study, we assessed change in preoperative to postoperative shoulder muscle activation in 10 patients over 6 months. Muscle activation was measured using 8 surface electrodes. Activation of the anterior, middle and posterior deltoid and surrounding muscles were recorded during shoulder abduction, flexion, external and internal rotation were quantified. One-way analysis of variance was used to identify significant differences in activation and time or speed. Least significant difference post hoc test was used to determine specific differences in muscle activation at subsequent time points. Results: RSA shoulders at 6 months postoperative showed a significant increase in activity of the middle deltoid predominantly. Middle deltoid activation increased during abduction (P < 0.001), flexion (P = 0.008), external (P < 0.001) and internal (P < 0.001) rotation. Conclusions: Our study demonstrates the middle deltoid predominates in rotator cuff function in RSA as defined by quantitative activation, significant involvement in all shoulder motions, and increased activation at subsequent times. These findings may help guide future RSA designs to optimize deltoid wrapping allowing for maximal strength and efficiency.