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The efficacy of Surgisis® anal fistula plug in closure of Crohn's anorectal fistula was studied.Patients with Crohn's anorectal fistulas were prospectively studied. Diagnosis was made by histologic, radiographic, or endoscopic criteria. Variables recorded were: number of fistula tracts (primary openings), presence of setons, and current antitumor necrosis factor therapy. Under general anesthesia and in prone jackknife position, patients underwent irrigation of the fistula tract by using hydrogen peroxide. Each primary opening was occluded by using a Surgisis® anal fistula plug. Superficial tracts amenable to fistulotomy were excluded.Twenty consecutive patients were prospectively enrolled, comprising a total of 36 fistula tracts. At final follow-up, all fistula tracts had been successfully closed in 16 of 20 patients, for an overall success rate of 80 percent. Thirty of 36 individual fistula tracts (83 percent) were closed at final follow-up. Patients with single fistulas (with 1 primary opening) were most likely to have successful closure using the anal fistula plug. Successful closure was not correlated with the presence of setons or antitumor necrosis factor therapy.Closure of Crohn's anorectal fistula tracts using Surgisis® anal fistula plug is safe and successful in 80 percent of patients and 83 percent of fistula tracts. Closure rates were higher with single tracts than complex fistulas with multiple primary openings.