Background: Reverse total shoulder arthroplasty (rTSA) offers tremendous promise for the treatment of complex pathologies beyond the scope of anatomic total shoulder arthroplasty but is associated with a higher rate of major postoperative complications. We aimed to design and validate a machine learning (ML) model to predict major postoperative complications or readmission following rTSA. Methods: We retrospectively reviewed California's Office of Statewide Health Planning and Development database for patients who underwent rTSA between 2015 and 2017. We implemented logistic regression (LR), extreme gradient boosting (XGBoost), gradient boosting machines, adaptive boosting, and random forest classifiers in Python and trained these models using 64 binary, continuous, and discrete variables to predict the occurrence of at least one major postoperative complication or readmission following primary rTSA. Models were validated using the standard metrics of area under the receiver operating characteristic (AUROC) curve, area under the precision-recall curve (AUPRC), and Brier scores. The key factors for the top-performing model were determined. Results: Of 2799 rTSAs performed during the study period, 152 patients (5%) had at least 1 major postoperative complication or 30-day readmission. XGBoost had the highest AUROC and AUPRC of 0.681 and 0.129, respectively. The key predictive features in this model were patients with a history of implant complications, protein-calorie malnutrition, and a higher number of comorbidities. Conclusion: Our study reports an ML model for the prediction of major complications or 30-day readmission following rTSA. XGBoost outperformed traditional LR models and also identified key predictive features of complications and readmission.