Background: Few studies have focused on the risk factors for failure to achieve fascial closure after use of negative-pressure wound therapy (NPWT) in an open abdomen (OA). We aimed at analyzing possible risk factors for failure of fascial closure and the risk of fistulas after nontrauma lower gastrointestinal (GI) tract surgery treated with OA. Methods: This retrospective study included 101 nontrauma patients treated with OA from 2007 to 2011. Multivariate analyses of risk factors were performed. Results: Indications for OA were diffuse peritonitis (n = 47), need for second look (n = 26), failure to achieve fascial closure (e.g., bowel edema) at primary laparotomy (n = 24), and fascial necrosis (n = 4). Of the 101 patients, 61 (60 %) were alive at discharge, with one death possibly related to OA (fistula from an iatrogenic perforation). Delayed fascial closure was obtained in 40 (66 %) of the surviving patients, with 80 % when the indications for OA was need for second look and 72 % in cases of diffuse peritonitis. Compared with need for second look [hazard ratio (HR = 1), 95 % CI], proportional HR for failure of delayed fascial closure were peritonitis 1.96 (1.10-3.49) and failure to achieve fascial closure at primary laparotomy 4.70 (2.17-10.2). In the presence of a stoma the HR was 2.02 (1.13-3.63). Conclusions: OA using NPWT seems to be a safe procedure, with few procedure-related complications. Failure of fascial closure is related to the indication of OA and the presence of a stoma. Prospective multicenter studies are needed to establish which patients with lower GI surgery benefit from OA.