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The natural history of a pouch-related fistula in terms of timing of its development and its impact on pouch survival is poorly defined.This study aimed to evaluate factors associated with the time of onset of ileoanal pouch–related fistulas and predictors of pouch failure after the development of fistulas.This study is an evaluation of prospectively collected data from a cohort of patients with pouch-related fistulas.Patients were identified from a prospective ileoanal pouch database, with data recorded from 1983 to 2009.Patients who participated had developed a fistula after ileoanal pouch surgery. Patients were classified according to the time of onset, origin, and target of pouch fistulas into “early” and late” groups.Ileoanal pouch failure was the main outcome measure.Three hundred six patients (158 early-onset, 148 late-onset) with 373 pouch-related fistulas were identified. The early-onset group had a higher mean body mass index (P = .013) and more patients in this group developed a postoperative leak (P < .001), whereas diagnosis revision to Crohn's disease was more frequent in the late-onset group (P = .018). Overall, pouch failure occurred in 89 (29%) patients. Major abdominal procedures were more common in the early-onset group (18 vs 6%). There was no difference in pouch failure between the early- and late-onset groups (P = .24). On multivariate analysis, a current Crohn's diagnosis (P < .001), major fistula (P = .022), history of colectomy before ileoanal pouch (P = .005), handsewn anastomosis (P = .008), anastomotic leak (P = .012), and body mass index over 30 (P = .018) were independent risk factors for failure. No individual risk factor for failure was separately associated with either early or late fistula groups.The timing and etiology of pouch fistula appear to be interrelated. There is a temporal association between procedure-related sepsis and early and delayed diagnosis of Crohn's disease and late fistula development. Cause of the fistula and associated factors rather than timing after IPAA is associated with long term pouch retention.