Introduction Shoulder arthroplasty with previous axillary lymph node dissection historically has unsatisfactory outcomes. We analyzed outcomes of primary shoulder arthroplasty in patients with previous axillary lymph node dissection. Methods Thirty-two primary shoulder arthroplasties after prior axillary lymph node dissection were performed. These patients were analyzed for patient-reported outcomes, range of motion, complications, and reoperations. Results Average age was 70.8 ± 7.5 years old. There were 19 anatomic total shoulder arthroplasties, four hemiarthroplasties, and nine reverse total shoulder arthroplasties. Eight were performed by a superior approach while 24 were performed by a deltopectoral approach with cephalic vein preservation. There were three complications (one deltoid dehiscence, one axillary nerve palsy, and one postoperative pneumonia). There was one revision (hemiarthroplasty to reverse total shoulder arthroplasty for cuff failure at 91 weeks), two reoperations, and no infections. Patient-reported outcomes were available for 21/26 (80.1%) of the surviving shoulders at 4.8 ± 2.0 years. Average visual analog scale pain score was 7.1 ± 14.5, Simple Shoulder Test score 8.3 ± 2.6 “yes” responses, Single Assessment Numeric Evaluation score 80.2 ± 17.4, and American Shoulder and Elbow Surgeons score 83.6 ± 14.1. Conclusion Axillary lymph node dissection is not a contraindication to shoulder arthroplasty. A deltopectoral exposure can be utilized without substantial risk of worsening lymphedema or wound complications. While a superior approach avoids cephalic vein injury, important approach-related complications (deltoid dehiscence and axillary nerve palsy) were observed. Level of evidence: Level IV—case series.