PURPOSE: Lateral partial internal sphincterotomy is considered as the best surgical procedure of the idiopathic chronic anal fissure. Because the aim of surgery is to relieve sphincter spasm, and occasional minor incontinence following surgery has been reported, alternative chemical means of spasmolysis could be considered. Nitric oxide (NO) is known to be a major inhibitory neurotransmitter of the internal anal sphincter, so we investigated the effect of topical nitroglycerin for chronic anal fissure. METHODS: Twenty nine patients (19 women, mean age 36 years) with chronic anal fissure were treated with 0.2% nitroglycerin ointment. Pain score was quantitated with Visual Analog Scale (VAS) in regular time interval. Manometry was performed in five patients and maximum anal resting pressure (MARP) was measured before and 30 minutes after topical application of nitroglycerin ointment. All patients were re-examined and questioned regarding pain relief and side effects 2 years after cessation of treatment. RESULTS: All had appearances of chronicity and pain. There were 25 posterior and 12 anterior fissures. Pain was significantly abolished within 5 minutes after application of nitroglycerin ointment. Mean pain score (VAS) was 6.03 before, 0.69 30 min after, 0.58 1 week after, and 0.53 3 weeks after application of nitroglycerin ointment (P<0.001). MARP was markedly reduced 30 minutes after application of nitroglycerin from 166.2 15.1 cmH2O to 108.8 20.9 cmH2O (P<0.05). The 57% of patients (13/23) were effective for 2 years and 22% of patients (5/23) had recurred their symptom after cessation of nitroglycerin ointment. Two patients (9%), whose fissures had not healed completely within 3 weeks were requested for surgery and the other 2 patients (9%) had been operate due to the side effect of the ointment. Mild headache (7%) and dizziness (10%) were occured, but well tolerated when the dose was reduced. CONCLUSIONS: Topical application of nitroglycerin ointment seems to be an effective and safe alternative in the treatment of chronic anal fissure.