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Mesh infection after abdominal hernia repair is a devastating complication that affects general and plastic surgeons alike. The purpose of this study was 3-fold: (1) to determine current evidence for treatment of infected abdominal wall mesh via systematic review of literature, (2) to analyze our single-institution experience with treatment of infected mesh patients, and (3) to establish a framework for how to approach this complex clinical problem.Literature search was performed using the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines, followed by single-institution retrospective analysis of infected mesh patients.A total of 3565 abstracts and 92 full-text articles were reviewed. For qualitative and quantitative assessment, articles were subdivided on the basis of treatment approach: “conservative management,” “excision of mesh with primary closure,” “single-stage reconstruction,” “immediate staged repair,” and “repair in contaminated field.” Evidence for each treatment approach is presented. At our institution, most patients (40/43) were treated by excision of infected mesh and single-stage reconstruction with biologic mesh. When the mesh was placed in a retrorectus or underlay fashion, 21.4% rate of hernia recurrence was achieved. Bridged repairs were highly prone to recurrence (88.9%; P = 0.001), but the bridging biologic mesh seemed to maintain domain and potentially contribute to a more effective repair in the future. Of the patients who underwent additional (“secondary”) repairs after recurrence, 75% were eventually able to achieve “hernia-free” state.This study reviews the literature and our single-institution experience regarding treatment of infected abdominal wall mesh. Framework is developed for how to approach this complex clinical problem.