The aim of this prospective study was to assess the effectiveness in healing anal fissure (AF) of lacidipine, a calcium channel blocker with a better tolerability in comparison to other calcium antagonists. Twenty-one consecutive patients (16 women, 76.2%) with AF (16 chronic, situated posteriorly in 17 patients (81.0%), anteriorly in 4) with a mean age of 37.1 years (SD, 13.6, range, 20-65) were treated with oral lacidipine (6 mg daily) and warm sitz baths for 28 days, adding only stool softeners for patients with constipation. Blood pressure, pain scores (assessed from 0 to 10 on a visual analogue scale) and fissure healing were monitored at 14 days, 28 days and 2 months. At the 14-day and 28-day follow-ups, the mean systolic and diastolic pressures were not significantly different from pre-treatment levels. Seven patients (33.3%) developed side effects, but only one, who developed dyplopia, withdrew from the study at the 14-day control (non-compliance rate with treatment, 4.8%). Pain scores were significantly reduced after 14 days and continued to show a significant reduction throughout the treatment period. Three fissures (14.3%) healed by 14 days and a total of 19 (90.4%) after 28 days: among the healed AF no recurrences were seen at the 2-month control. Among the two treatment failures, one was the patient who withdrew from the study at the 14-day control due to dyplopia and the other was a patient who failed to heal up to the 2-month follow-up, although completely asymptomatic. Both patients underwent left lateral sphincterotomy and healed. In conclusion, oral lacedipine is quite well tolerated and may offer a promising alternative treatment for AF.