Background Reverse total shoulder arthroplasty (RTSA) is widely used; however, the effects of RTSA geometric parameters on joint and muscle loading, which strongly influence implant survivorship and long-term function, are not well understood. By investigating these parameters, it should be possible to objectively optimize RTSA design and implantation technique. Questions/purposes The purposes of this study were to evaluate the effect of RTSA implant design parameters on (1) the deltoid muscle forces required to produce abduction, and (2) the magnitude of joint load and (3) the loading angle throughout this motion. We also sought to determine how these parameters interacted.Methods Seven cadaveric shoulders were tested using a muscle load-driven in vitro simulator to achieve repeatable motions. The effects of three implant parameters-humeral lateralization (0, 5, 10 mm), polyethylene thickness (3, 6, 9 mm), and glenosphere lateralization (0, 5, 10 mm)-were assessed for the three outcomes: deltoid muscle force required to produce abduction, magnitude of joint load, and joint loading angle throughout abduction. Results Increasing humeral lateralization decreased deltoid forces required for active abduction (0 mm: 68% ± 8% [95% CI, 60%-76% body weight (BW)]; 10 mm: 65% ± 8% [95% CI, 58%-72 % BW]; p = 0.022). Increasing glenosphere lateralization increased deltoid force (0 mm: 61% ± 8% [95% CI, 55%-68% BW]; 10 mm: 70% ± 11% [95% CI, 60%-81% BW]; p = 0.007) and joint loads (0 mm: 53% ± 8% [95% CI, 46%-61% BW]; 10 mm: 70% ± 10% [95% CI, 61%-79% BW]; p \ 0.001). Increasing polyethylene cup thickness increased deltoid force (3 mm: 65% ± 8% [95% CI, 56%-73% BW]; 9 mm: 68% ± 8% [95% CI, 61%-75% BW]; p = 0.03) and joint load (3 mm: 60% ± 8% [95% CI, 53%-67% BW]; 9 mm: 64% ± 10% [95% CI, 56%-72% BW