Background: Indications for reverse total shoulder arthroplasty (RTSA) have been expanding. In addition to degenerative joint disease (DJD), RTSA is now being used to treat proximal humerus fractures (PHF). The purpose of this study was to compare postoperative complications in RTSA performed for DJD versus PHF. Methods: A retrospective analysis of the PearlDiver National Database was performed. International Classification of Diseases 10 codes were used to identify RTSA patients from 2015-2018 and separate them into DJD and PHF cohorts. Demographics, comorbidities, and hospital data were identified and compared using a two-sample t-test and chi-squared test. Systemic complications at 90 days and surgical complications at 90 days, 1 year, and 2 years were compared using multivariable logistic regression. Results: Fifteen thousand six hundred seventy eight patients (92.6% DJD, 7.4% PHF) were identified. PHF patients were more likely to be older (70.3 vs. 69.7 years, P = .026), female (83.5% vs. 62.2%, P < .001), and have more medical comorbidities (Charlson Comorbidity Index 3.42 vs. 3.17, P = .006) than DJD patients. After controlling for patient factors, PHF patients were more likely than DJD patients to develop urinary tract infection (odds ratio [OR] 1.65, P < .001), deep vein thrombosis (OR 1.76, P = .024), and hematoma (OR 3.83, P < .001) within 90 days of RTSA. At 90 days, 1 year, and 2 years postoperatively, RTSA for PHF patients were also more likely than RTSA for DJD patients to sustain a periprosthetic fracture (OR 2.57, P < .001) and instability (OR 2.02, P < .001). Conclusions: Patients with DJD and PHF undergoing RTSA represent different patient populations with distinct postoperative clinical outcomes. RTSA for PHF has inferior outcomes, which is significant in an era of bundled payments.