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This study aimed to determine the risk of ileal pouch-anal anastomosis failure and factors predictive of failure overall and in patients with septic complications.Patients were identified through a prospectively maintained patient registry. All patients registered in the Mount Sinai Hospital Inflammatory Bowel Disease database who had an ileal pouch-anal anastomosis for more than 12 months were included in the study. Pouch failure was defined as ileal pouch-anal anastomosis excision or permanent diversion. Cox proportional hazard models with death as a competing risk were created, modeling time to failure as the outcome of interest for all patients and for the subgroup of patients with septic complications.The study included 1,554 patients. One hundred six patients experienced an ileal pouch-anal anastomosis failure (6.8%), 49 (46.2%) of these failures were caused by septic complications. Independent predictors of failure included Crohn’s disease (hazard ratio 7.5, 95% confidence interval [4.7, 12.0]) and postoperative sepsis (hazard ratio 6.6, 95% confidence interval [4.4, 9.8]). In the subgroup of patients with failure due to postoperative septic complications, independent predictors of failure were Crohn’s disease (hazard ratio 2.7, 95% confidence interval [1.3, 5.7]) and presence of a pouch fistula (hazard ratio 2.6, 95% confidence interval [1.3, 5.2]).Septic complications are the most common cause of ileal pouch-anal anastomosis failure. Careful patient selection and the prevention of septic complications may decrease the risk of this failure.