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Breast reconstruction with tissue expanders is the most common mode of reconstruction following mastectomy. Infection necessitating tissue expander removal is a significant complication leading to patient distress and increased health care costs.Over 3 years, 127 breast reconstructions with tissue expanders were performed by a single surgeon. Fifty-nine of these reconstructions were performed using a standardized protocol in which patients washed with chlorhexidine several days before surgery and received intravenous antibiotics preoperatively. Intraoperatively, the submuscular pocket was irrigated with triple-antibiotic solution and the skin was prepared again with povidone-iodine before expander placement. This group was referred to as the preintervention group. Sixty-eight of the reconstructions were performed using the standardized protocol with the addition of biodegradable antibiotic beads (Stimulan with vancomycin and gentamicin) in the submuscular pocket. This group made up the postintervention group. The primary outcome was the rate of infection necessitating tissue expander removal.The rate of tissue expander loss caused by infection was 11.9 percent in the preintervention group and 1.5 percent in the postintervention group (p = 0.024). Higher body mass index was associated with a statistically significant increase in infections necessitating expander removal.The use of absorbable antibiotic beads in the submuscular pocket reduced the risk of periprosthetic implant infection necessitating implant removal by 8-fold.Therapeutic, III.