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Botulinum toxin heals only approximately one-half of glyceryl trinitrate-resistant chronic anal fissures, perhaps because chemical sphincterotomy alone treats internal sphincter spasm but not chronic fissure fibrosis. We aimed to assess whether a novel procedure, fissurectomy-botulinum toxin, improves the healing rate of medically resistant fissures over that achieved with botulinum toxin alone.A prospective pilot study of chronic fissure patients failing medical therapy was undertaken. Fissurectomy was performed, with excision of the fibrotic fissure edges, curetting of the fissure base, and excision of the sentinel pile if present. Twenty-five units of botulinum toxin (Botox™) were injected into the internal sphincter. The primary end point was fissure healing, and secondary end points were improvement in symptoms, need for lateral internal sphincterotomy, and side effects.Thirty patients underwent fissurectomy-botulinum toxin (57 percent female; median age, 39 years). Nineteen patients had failed glyceryl trinitrate, whereas 11 had failure of both glyceryl trinitrate and botulinum toxin. At a median of 16.4 weeks follow-up, 28 fissures (93 percent) were healed. Two fissures (7 percent) remained unhealed but were symptomatically better and avoided lateral internal sphincterotomy. Two patients (7 percent) experienced transitory flatus incontinence.Fissurectomy-botulinum toxin heals over 90 percent of fissures resistant to medical therapy. Fissurectomy-botulinum toxin allows patients with medically resistant fissures to achieve a high rate of healing while avoiding the risk of incontinence associated with lateral internal sphincterotomy.