BACKGROUND: Periprosthetic infections represent major complications in breast reconstruction, frequently leading to expander-implant loss. No consensus regarding a management algorithm for attempted salvage currently exists. This study assessed outcomes of the authors' salvage protocol using an antibiotic-impregnated polymethylmethacrylate implant with expander device exchange. METHODS: A retrospective chart review identified infected implant-based breast reconstruction cases treated between 2009 and 2017. Of 626 cases initially identified, a total of 62 cases had severe prosthetic infections, and underwent either prosthetic salvage (n = 45) or immediate explantation (n = 17). All the prosthetic salvage patients received intravenous antibiotics followed by surgical débridement, insertion of polymethylmethacrylate plates, device exchange, and postoperative antibiotics. After clinical resolution of infection, tissue expansion was performed, with the polymethylmethacrylate plates remaining in situ until exchanged for permanent implants. RESULTS: The authors' study demonstrated a primary infection clearance rate of 82.2 percent (n = 37). Compared to the traditional explantation group, a significantly higher percentage of the salvage patients completed final reconstruction (84.4 percent versus 35.3 percent; p < 0.001). Fewer patients abandoned reconstruction efforts after infection clearance (2.2 percent versus 58.8 percent; p < 0.001). The majority of cases (78.8 percent) that succeeded the salvage protocol ultimately received implant-based reconstruction; 62.5 percent that failed the salvage protocol still went on to receive autologous tissue reconstruction. CONCLUSIONS: Sustained local antibiotic delivery using polymethylmethacrylate implants and expander device exchange can successfully salvage an infected breast expander/implant. Compared with the traditional explantation approach, more patients complete final reconstruction. Other benefits include preserved skin envelope integrity and possibly improved long-term aesthetic outcomes. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.