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Background: Reverse total shoulder arthroplasty (RTSA) has become an increasingly popular surgery for patients with rotator cuff arthropathy, unreconstructible proximal humeral fracture, and end-stage glenohumeral arthritis. The increased annual volume of RTSAs has resulted in more postoperative complications and revision rates between 3.3% and 10.1%. Postoperative infection is one of the most common complications requiring revision surgery after primary RTSA. This study assesses patient-specific risk factors for development of early infection after primary RTSA in a single high-volume shoulder arthroplasty institution. Methods: From 2014 to 2019, 902 consecutive primary RTSAs were performed for surgical treatment of rotator cuff arthropathy, glenohumeral arthritis, inflammatory arthropathy, and/or dislocation. Excluding proximal humeral or scapula fractures, 756 cases met the inclusion criteria and had a minimum of 3-month follow-up. All surgeries were performed using the same surgical technique and received similar antibiotic prophylaxis. Age, patient demographics, medical history, smoking history, and prior ipsilateral shoulder treatment and/or surgery were recorded. Multivariable logistic regression analysis was used to determine risk factors associated with development of postoperative shoulder infection. Results: Thirty-five patients did not meet minimum follow-up criteria and were lost to follow-up. Overall, of 721, 22 patients (3%) developed a postoperative ipsilateral shoulder infection. Previous nonarthroplasty surgery and history of rheumatoid arthritis were significantly associated with the development of postoperative shoulder infection. Amongst 196 patients who had previous nonarthroplasty shoulder surgery, there were 12 postoperative shoulder infections (6%) compared with those without previous shoulder surgery (10 of 525, 2%) (P = .003). Among 58 patients with rheumatoid arthritis, there were 5 postoperative shoulder infections (9%) compared with patients without rheumatoid arthritis (17 of 663, 3%) (P = .010). Patient age, gender, smoking status, history of diabetes mellitus, history of cancer/immunosuppression, and prior cortisone injection did not demonstrate significant associations with the development of postoperative infection. Conclusion: Prior nonarthroplasty shoulder surgery and/or rheumatoid arthritis are independently associated with the development of postoperative infection after primary RTSA. Patients who demonstrate these risk factors should be appropriately evaluated and preoperatively counseled before undergoing primary RTSA. Strong consideration should be given to avoid minimally invasive nonarthroplasty surgery as a temporizing measure to delay definitive RTSA.