BackgroundThe leading cause of pouch failure following ileal pouch-anal anastomosis are peri-pouch fistulas and pelvic sepsis. ObjectiveDetermine the overall efficacy of current surgical therapy for the treatment of perianal and anovaginal fistulizing disease related to Crohn’s disease phenotype of the pouch. DesignRetrospective cohort study of a prospectively maintained, IRB-approved database. Settings/PatientsNinety-one (2.3%) patients of 3058 patients with an original diagnosis of ulcerative colitis who underwent proctocolectomy with ileal pouch-anal anastomosis between 2000 and 2021 at the Cleveland Clinic and underwent postoperative surgery for Crohn’s-related perianal disease. InterventionsTwo hundred thirty-one operations for perianal or anovaginal fistula(s). Main Outcome and MeasuresHealing rate of surgical therapy for peri-pouch fistulizing disease, impact of recurrent interventions on outcomes, and predictors of surgical failure. ResultsOverall mean age was 39.1 (± 11.6) years, with a BMI of 25.3 (± 6.3) kg/m2. More than half of the patients were female (n = 52, 57.1%). Sixty-three patients (69.2%) had a perianal fistula, 25 (27.5%) had an anovaginal fistula, and 3 (3.3%) patients had both. Overall success rate for healing was 59.3% (n = 54/91) at a mean follow-up of 6.4 (± 4.8) years. Seventeen (18.7%) patients underwent a concomitant diverting loop ileostomy. Among them, eight (47.0%) patients had the ileostomy closure after a mean time of 9.7 (± 2.8) months. In the multivariable logistic regression model, patients who had seton insertions in any operation were significantly less likely to heal (OR 0.11 95%, CI 0.03–0.43, p = 0.001). Overall pouch failure rate was 12.1%. LimitationsRetrospective single-center study which lacks a control arm and consistent long-term follow-up specific to a population-based dataset. ConclusionsPouch patients who develop perianal disease are difficult to treat, sometimes requiring pouch excision. However, when medical treatment alone is not effective, a multidisciplinary approach including surgical intervention can result in complete fistula healing in more than half of the cases.