Background & objectives Infected pancreatic necrosis (IPN) is associated with increased morbidity and mortality. Gut barrier dysfunction has been shown to increase the risk of bacterial translocation from the gut into the pancreatic bed. The primary aim of the study is to evaluate if ileus, a clinical marker of gut barrier dysfunction, can predict the development of IPN. Methods A retrospective cohort study of patients with necrotizing pancreatitis (NP) was conducted from 2000 to 2014. Ileus was defined as ≥2 of the following criteria: nausea/vomiting; inability to tolerate a diet, absence of flatus, abdominal distension and features of ileus on imaging. Extensive necrosis was defined as >30% nonenhancing pancreatic parenchyma on contrast-enhanced CT. Multivariable cox proportional hazard analysis was used to evaluate known and potential predictors of IPN. Results 142 patients were identified with NP, 61 with IPN and 81 with sterile necrosis. In comparison to a diagnosis of ileus documented in the medical chart, the ileus criteria had a sensitivity, specificity and positive and negative predictive value of 100%, 93%, 78% and 100%, respectively. On multivariate cox proportional hazard analysis, ileus [HR:2.6; 95%CI:1.4–4.9] and extensive necrosis [HR:2.8; 95%CI:1.3–5.8] were independently associated with the development of IPN while there was no association with bacteremia [HR:1.09; 95%CI:0.6–2.1]. Conclusion Ileus in NP can be accurately defined using surgical criteria. Ileus is independently associated with the future development of IPN. Further studies will be needed to determine if ileus can serve as a clinical marker to direct therapeutic interventions aimed at reducing the incidence of IPN.