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Background: Use of a prosthetic mesh for repair of incisional hernias reduces hernia recurrence. Mesh infection, the dreaded complication of hernia repair, results in significant morbidity and challenges for subsequent abdominal wall reconstruction. The attributable risk factors that lead to mesh explantation are not well known.Methods: This is a multisite cohort study of all patients undergoing incisional hernia repair at 16 VA hospitals from 1998 to 2002. Pre-operative risk factors, hernia presentation and intra-operative variables as well as repair technique, were assessed for association with subsequent mesh explantation. Log rank and Cox Proportional Hazards Model were used to determine significant predictors of mesh explanation following repair.Results: Of the 1,071 mesh repairs, 55 (5.1%) had subsequent mesh explantation at a median of 7.3 months (IQR 1.4-22.2 months) following hernia repair with permanent mesh prosthesis. Reasons for explantation were mesh infection (69%), other mesh problem such as intestinal obstruction (24%), or explantation at subsequent surgical procedure unrelated to mesh repair (7%). Factors significantly associated with mesh explantation on univariate analyses were repair of recurrent hernia with prior mesh placement (8.3%, p<0.03), concomitant intra-abdominal procedure with hernia repair (17.7%, p<0.0001), intra-operative enterotomy (15.1%, p<0.0001). The occurrence of a post-operative surgical site infection resulted in a 20.6% mesh explantation rate. No difference among types of repair; laparoscopic, or open onlay, inlay or underlay were observed. Cox proportional hazards modeling found same site concomitant surgery (O.R. = 3.59, 95% C.I. 1.68, 7.69) and post-operative surgical site infection (O.R. = 4.90, 95% C.I. 2.58, 9.31) were independently associated with mesh explantation.Conclusions: Patients undergoing incisional hernia repair with intentional or unintentional intestinal procedures have a greater than three-fold increased risk of subsequent mesh explantation. The use of a permanent prosthetic mesh should be used with caution in this setting. The development of a post-operative surgical site infection also strongly predicts subsequent mesh explantation.