Background: Prosthetic mesh used for incisional hernia repair (IHR) reduces hernia recurrence. Mesh infection results in significant morbidity and challenges for subsequent abdominal wall reconstruction. The risk factors that lead to mesh explantation are not well known. Methods: This is a multisite cohort study of patients undergoing IHR at 16 Veterans Affairs hospitals from 1998 to 2002. Results: Of the 1,071 mesh repairs, 55 (5.1%) had subsequent mesh explantation at a median of 7.3 months (interquartile range 1.4-22.2) after IHR with permanent mesh prosthesis. Infection was the most common reason for explantation (69%). No differences were observed by the type of repair. Adjusting for covariates, same-site concomitant surgery (hazard ratio [HR] = 6.3) and postoperative surgical site infection (HR = 6.5) were associated with mesh explantation. Conclusions: Patients undergoing IHR with concomitant intra-abdominal procedures have a greater than 6-fold increased hazard of subsequent mesh explantation. Permanent prosthetic mesh should be used with caution in this setting. © 2011 Published by Elsevier Inc.