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The study analyzed clinical trials investigating the effectiveness of diltiazem (DTZ) and glyceryltrinitrate (GTN) for the nonsurgical management of chronic anal fissure (CAF).Randomized trials on the effectiveness of DTZ and GTN were analyzed systematically using RevMan® where combined outcome was expressed as risk ratio (RR).Seven randomized controlled trials that included 481 patients were analyzed. Two-hundred and thirty-eight patients were treated with DTZ and 243 patients were treated with GTN. There was significant heterogeneity [Tau2 = 0.24, χ2 = 13.16, d.f. = 6 (P < 0.05); I2 = 54%] among the included trials. In the random-effects model, DTZ was associated with a lower incidence of side effects (RR = 0.48; 95% CI = 0.27, 0.86; z = 2.46; P < 0.01), headache (RR = 0.39; 95% CI = 0.24, 0.66; z = 3.54; P < 0.004) and recurrence (RR = 0.68; 95% CI = 0.52, 0.89; z = 2.77; P < 0.006) of CAF. Both GTN and DTZ were equally effective (RR = 1.10; 95% CI = 0.90, 1.34; z = 0.92; P = 0.36) in the nonsurgical management of CAF.This systematic review of seven trials validates and strengthens the finding of a previously published meta-analysis of two randomized trials. Both DTZ and GTN are equally effective in the management of CAF. However, DTZ is associated with a lower incidence of headache and recurrent fissure. Therefore DTZ should be the preferred first line of treatment for CAF.