PURPOSE:Both topical diltiazem, a calcium channel blocker, and glyceryl trinitrate, a nitric oxide donor, lower anal pressure and heal two‐thirds of chronic anal fissures. This study evaluated the efficacy of diltiazem for fissures that failed to heal with glyceryl trinitrate.METHODS:Consecutive patients with persistent chronic fissures despite treatment with 0.2 percent glyceryl trinitrate ointment underwent anal manometry before and for 1 hour after application of 700 mg of 2 percent diltiazem gel to the distal anal canal. Patients applied diltiazem twice daily for eight weeks or until the fissure had healed. At fortnightly review, fissure healing was assessed, and side effects were noted. Patients scored symptoms of pain, bleeding, and irritation using linear visual analog scales at the initial and follow‐up visits.RESULTS:In 39 patients (13 males; median age, 42 (range, 20‐ 80) years), topical 2 percent diltiazem gel lowered anal resting pressure by 20 percent from a median of 93 to 74 cm H2O (P< 0.0001, Wilcoxon), and fissures healed in 19 (49 percent) within 8 weeks. Before diltiazem, 27 patients (69 percent) had used a complete course of glyceryl trinitrate (0.5 g twice daily for 8 weeks), and 12 (44 percent) of these healed with diltiazem. The remaining 12 patients had discontinued glyceryl trinitrate prematurely or used less because of headaches; 7 (58 percent) of these healed with diltiazem, and 5 (42 percent) did not. Side effects occurred in four patients (10 percent): three reported perianal itching but continued with treatment, and one developed headaches, drowsiness, and mood swings six weeks into treatment and stopped diltiazem at that time.CONCLUSION:Topical 2 percent diltiazem is effective treatment for glyceryl trinitrate‐resistant chronic anal fissures. Side effects, mainly perianal itching, may occur in 10 percent of patients but are generally tolerated.