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Between 1972 and 1994, 2279 patients underwent primary shoulder arthroplasty (2512 shoulders) and 194 patients underwent revision shoulder arthroplasty (222 shoulders) at the authors’ institution. Of these, 18 patients with primary shoulder arthroplasties (19 shoulders) and seven patients with revision shoulder arthroplasties (seven shoulders) were diagnosed with deep periprosthetic infection. Additionally, during this period, seven patients (seven shoulders) with primary shoulder arthroplasties and one patient (one shoulder) with a previously revised shoulder arthroplasty were referred to the authors’ institution for treatment of deep periprosthetic infection. Two patients (two shoulders) were excluded because of incomplete medical records and with component removal performed elsewhere. The average time from arthroplasty to the diagnosis of infection was 3.5 years (range, 0–14.8 years). The patients were divided into four groups on the basis of treatment. Group I comprised 20 patients (21 shoulders) who underwent resection arthroplasty. Six of the 21 shoulders had additional episodes of infection. Group II comprised six patients (six shoulders) who underwent debridement and prosthetic retention. Three of the six shoulders failed this treatment with subsequent reinfection and underwent a resection arthroplasty. Group III comprised two patients (two shoulders) who had removal of the prosthesis, debridement, and immediate reimplantation. One patient underwent resection arthroplasty 9 months after direct exchange because of reinfection. Group IV comprised three patients (three shoulders) who had removal of the prosthesis, debridement, and delayed reimplantation. Reinfection has not occurred in any of these patients. At final followup, patients with a prosthesis in situ had better pain relief and shoulder function than patients treated with resection arthroplasty. Delayed reimplantation may offer the best hope for pain relief, eradication of infection, and maintenance of shoulder function.