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Background: The development of a deep wound infection in the presence of hardware after open reduction and internal fixation presents a clinical dilemma, and there is scant literature to aid in decision-making. The purpose of the present study was to determine the prevalence of osseous union with maintenance of hardware after the development of postoperative infection within six weeks after internal fixation of a fracture. Methods: The present study included 121 patients from three level-I trauma centers, retrospectively identified from billing and trauma registries, in whom 123 postoperative wound infections with positive intraoperative cultures had developed within six weeks after internal fixation of acute fractures. The incidence of fracture union without hardware removal was calculated, and the parameters that predicted success or failure were evaluated. Results: Eighty-six patients (eighty-seven fractures; 71%) had fracture union with operative debridement, retention of hardware, and culture-specific antibiotic treatment and suppression. Predictors of treatment failure were open fracture (p = 0.03) and the presence of an intramedullary nail (p = 0.01). Several variables were not significant but trended toward an association with failure, including smoking, infection with Pseudomonas species, and involvement of the femur, tibia, ankle, or foot. Conclusions: Deep infection after internal fixation of a fracture can be treated successfully with operative debridement, antibiotic suppression, and retention of hardware until fracture union occurs. These results may be improved by patient selection based on certain risk factors and the specific bacteria and implants involved. Level of Evidence: Therapeutic Level IV. See Instructions to Authors for a complete description of levels of evidence.