Background: Fissure-in-Ano is a common condition of the anorectal region. Most of the time, it is managed non-surgically. There are various drugs used for the treatment of anal fissures. Calcium channel blockers are one of them that reduce the tone of sphincter muscles. The present study compares the efficacy of oral diltiazem and topical 2% diltiazem ointment in patients with chronic anal fissures. Methods: Patients were randomized into two groups. Group A (n=25) received treatment in the form of oral diltiazem, while group B (n=25) received treatment in the form of 2% (weight/volume) diltiazem ointment for local application in addition to other conservative methods like sitz bath and stool softeners. Outcomes in the form of success of treatment and complications were assessed. Statistical analysis was done using MedCalc software version 14.0. P value of<0.05 was considered significant. Results: The mean age of patients was 32.00±10.67 years in group A and 30.64±9.53 years in group B. Pain relief was significantly better in group B than in group A at the end of the first week (P=0.00018), but at the end of 6th week, no significant difference was observed. Fissure healing was more significant in group B than in group A after 6 weeks (P=0.0152). Conclusion: Local diltiazem ointment is a better option than oral diltiazem for anal fissures with respect to better outcomes and lesser complications.