Primary colonic anastomosis in trauma patients has been demonstrated to be safe. However, few studies have investigated this in the setting of damage control laparotomy. We hypothesized that colonic anastomosis for trauma patients requiring an open abdomen (OA) would have a higher anastomotic leak (AL) rate when compared with patients having an immediate abdominal closure following trauma laparotomy. We performed a cohort comparison study of all trauma patients who underwent colectomy, between the years 2004 and 2009. Exclusion criteria were mortality within 24 hours of admission or colectomy for indications unrelated to injury. Data collected included age, gender, injury severity score, mechanism, length of stay, and mortality. Multivariable logistic regression was performed to assess the relationship of OA to our primary outcome measure, AL. Totally, 174 patients met study criteria. Fecal diversion was performed in 58 patients, and colonic anastomosis was performed in the remaining 116 patients. Patients with OA had a clinically significant increase in AL rate compared with immediate abdominal closure (6% vs. 27%, p=0.002). Logistic regression demonstrated that OA was independently associated with AL, with OA patients having more than a sixfold increase in odds of AL compared with those who were closed (odds ratio=6.37, p=0.002, area under the receiver operator curve=0.72). Transfusion requirement and left-sided anastomosis were risk factors for leak. Patients with a colonic anastomosis and an OA have an unacceptably high leak rate compared with those who undergo reconstruction with immediate closure. Given the significant risk of AL, colonic anastomosis should not be routinely performed in patients with OA.