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Infliximab is an effective treatment for active intestinal Crohn's disease; however, the efficacy of infliximab in perianal Crohn's disease is controversial. This study was designed to compare patients with Crohn's disease who underwent perianal fistula surgery with or without infliximab infusion.A retrospective chart review of 226 consecutive patients with Crohn's disease who underwent operative treatment with or without infliximab (3-6 infusions of 5 mg/kg) from March 1991 through December 2005 was completed. Patients were classified as completely healed, minimally symptomatic (seton placement with minimal drainage and/or infliximab dependence), and failure (persistent or recurrent symptomatic fistula, diverting procedure, or proctectomy).A total of 226 patients underwent operative treatment alone (n = 147) or in combination with infliximab infusion (n = 79). Age, gender, and preoperative history of intestinal and perianal Crohn's disease were similar between groups. Mean follow-up was 30 (range, 6-216) months. Operative treatment consisted of seton drainage (n = 112), conventional fistulotomy (n = 92), fibrin glue injection (n = 14), advancement flap (n = 5), collagen plug insertion (n = 2), and transperineal repair (n = 1). Eighty-eight patients (60 percent) healed completely with operative treatment alone, and 47 patients (59 percent) healed after operative treatment in combination with infliximab (P= not significant).Operative treatment of perianal fistulas in patients with Crohn's disease resulted in complete healing in approximately 60 percent of patients. Preoperative infliximab infusion did not affect overall healing rates.