The safety of arthroplasty in patients with a previous periprosthetic joint infection (PJI) remains unclear. The objective of this study was to determine whether patients with a history of a properly treated PJI complicating lower extremity arthroplasty can safely undergo shoulder arthroplasty without an increased risk of shoulder infection or compromise in their clinical outcomes. Between 2002 and 2013, 36 patients with successful treatment of an infected lower extremity arthroplasty underwent a subsequent primary shoulder arthroplasty. Three were lost to follow-up. The remaining 33 shoulders were analyzed at a mean follow-up of 3.5 years for radiographic, clinical, and functional outcomes. Nine patients were receiving chronic antibiotic suppression at the time of their index shoulder arthroplasty. The mean time between PJI treatment and shoulder arthroplasty was 4.7 years (range, 0.7-13.1 years). Shoulder arthroplasty led to improved pain scores and range of motion. Excellent or satisfactory modified Neer ratings were achieved in 78.8% of patients. There was no difference in American Shoulder and Elbow Surgeons scores between the groups with and without chronic antibiotic suppression. There were 2 reoperations, both in patients not receiving chronic suppression. The indications were aseptic glenoid loosening and infection after a periprosthetic fracture. The final estimated survival free of infection was 93.3%. Shoulder arthroplasty in patients with a history of PJI complicating hip or knee arthroplasty seems to be safe, with a low rate of infection. Thus, previous lower extremity PJI should not be considered a relative contraindication to shoulder arthroplasty.