Background: Substantial proximal humeral bone loss may compromise reverse shoulder arthroplasty secondary to limited implant support, insufficient soft tissue tension due to shortening, lack of attachment sites for the posterosuperior cuff when present, and lack of lateral offset of the deltoid. In these circumstances, use of a proximal humeral replacement may be considered. Patients/Methods: Between 2012 and 2014, 34 consecutive reverse shoulder arthroplasties were performed using a proximal humeral replacement system. The indications were failed shoulder arthroplasty (15), oncology reconstruction (9), humeral malunion/nonunion (7), prior resection arthroplasty (2), and intraoperative fracture (1). All patients were included in the survival analysis. Twenty-two patients with minimum 2-year follow-up were included in analysis of clinical results. Results: Among the cohort of 34 patients, there were 8 additional reoperations: humeral loosening (3), periprosthetic fracture (2), irrigation and debridement (2), and glenoid loosening (1). Humeral component loosening occurred exclusively in patients undergoing revision shoulder arthroplasty. The 4 patients had an average 3.75 prior procedures before the proximal humeral replacement. Two of the revisions were from cemented to uncemented stems. Among the 23 patients with minimum 2-year follow-up, there was significant improvement in pain scores (4.1 vs 0.6), forward elevation (31 vs 109) degrees, and 81% were satisfied. Conclusion: Use of a proximal humeral replacement when performing a reverse shoulder arthroplasty in the complex setting of substantial proximal humerus bone loss provides good clinical results and a particularly low dislocation rate. However, the rate of loosening of the humeral component in the revision setting suggests that proximal humeral replacement components should be cemented when revising a previously cemented stem. IRB: 16-006966.