Reverse shoulder arthroplasty (RSA) is commonly used to treat glenohumeral arthritis in patients with rotator cuff tears. RSA has an associated risk of instability and weakening in internal rotation (IR), but the underlying biomechanics driving this is unknown. Lack of intact subscapularis post-RSA may contribute to weakness, but some clinical studies suggest influence of subscapularis repair may depend on glenohumeral center of rotation (COR) following lateralized RSA. Our goal was to examine subscapularis IR functional capacity and whether it is affected by joint center of rotation following RSA using computational biomechanical simulation and an existing validated model of the upper limb. To simulate COR position after RSA, glenohumeral COR was translated medially from 0-30mm along the scapular spine axis, as well as 10mm inferior and superior, to capture traditional and lateralized COR locations. Subscapularis moment-generating capacity, moment arm, force-generating capacity, and muscletendon length were computed over -40° to 40° shoulder axial rotation (IR: positive) in neutral abduction. Subscapularis moment-generating capacity decreased with IR. Moment-generating capacity was minimally affected by COR >10mm medial displacement, with larger decreases as COR medialized from native COR. Subscapularis moment arm was minimally affected in medial COR locations; peak moment arm was 0.7mm higher for the 30mm medial COR compared to the intact shoulder. Tendon force decreased markedly with more medial COR. The 10mm, 20mm and 30mm medial COR positions exhibited decreased mean force of 144N, 412N and 565N from native, respectively. Subscapularis muscle-tendon length decreased with medialized COR. Changes were most marked in 25°-40° IR. Simulations suggest that although subscapularis moment arm increases as shoulder COR becomes more medial, force-generating capacity decreases due to muscle slackening. Thus, net effect of COR on subscapularis momentgenerating capacity is minimal except in the most medial location. This is consistent with a cadaver study of 4 RSA configurations which reported that IR and ER are not significantly affected by lateralization. However, a prior clinical study reported declines in American Shoulder and Elbow Surgeons (ASES) score 2 years post-RSA with a lateralized repair when subscapularis repair is also performed; ASES score is correlated with shoulder abduction, flexion, internal and external rotation moment-generating capacity. Although subscapularis IR moment may be unaffected by lateralization, other consequences of lateralization, such as changes to joint reaction force or adduction moment, may explain these clinical observations.