Background: Recent studies report the safety and feasibility of performing delayed anastomosis (DA) in patients undergoing damage control laparotomy (DCL) for destructive colon injuries (DCIs). Despite accumulating experience in both civilian and military trauma, questions regarding how to best identify high-risk patients and minimize the number of anastomosis-associated complications remain. Our current practice is to perform a definitive closure of the colon during DCL, unless there is persistent acidosis, bowel wall edema, or evidence of intra-abdominal abscess. In this study, we evaluated the safety of this approach by comparing outcomes of patients with DCI who underwent definitive closure of the colon during DCL versus patients managed with colostomy with or without DCL. Methods: We performed a retrospective chart review of patients with penetrating DCI during 2003 to 2009. Severity of injury, surgical management, and clinical outcome were assessed. Results: Sixty patients with severe gunshot wounds and three patients with stab wounds were included in the analysis. DCL was required in 30 patients, all with gunshot wounds. Three patients died within the first 48 hours, three underwent colostomy, and 24 were managed with DA. Thirty-three patients were managed with standard laparotomy: 26 patients with primary anastomosis and 7 with colostomy. Overall mortality rate was 9.5%. Three late deaths occurred in the DCL group, and only one death was associated with an anastomotic leak. Conclusions: Performing a DA in DCI during DCL is a reliable and feasible approach as long as severe acidosis, bowel wall edema, and/or persistent intra-abdominal infections are not present.