The aim of this prospective study was to assess the efficacy of different medical treatments and surgery in the treatment of chronic anal fissure (CAF). From 1/04 to 09/06, 156 patients with typical CAF completed the study. All patients were treated with 0.2% nitroglycerin ointment (GTN) or anal dilators (DIL) for 8 weeks. If no improvement was observed after 8 weeks, patient was assigned to the other treatment or a combination of the two. Persisting symptoms after 12 weeks or recurrence were indications for either botulinum toxin injection into the internal sphincter and fissurectomy or lateral internal sphincterotomy (LIS). During the follow-up (19 +/- 8 months), healing rates, symptoms, incontinence scores, and therapy adverse effects were prospectively recorded. Overall healing rates were 65.3 and 96.3% after GTN/DIL or BTX/LIS. Healing rate after GTN or DIL were 39.8 and 46%, respectively. Thirty-six patients (23.1%) responded to further medical therapy. Fifty-four patients (34.6%) underwent BTX or LIS. Healing rate after BTX was 81.8%. LIS group showed a 100% healing rate with no morbidity and postoperative incontinence. In conclusion, although LIS is far more effective than medical treatments, BTX injection/fissurectomy as first line treatment may significantly increase the healing rate while avoiding any risk of incontinence.