OBJECTIVE: This study aims to compare the short- and long-term outcomes of botulinum toxin (BT) alone versus BT combined with topical diltiazem (TD) in the treatment of chronic anal fissures (CAF). DESIGN: The study is designed as a retrospective analysis, reviewing data from 1296 patients diagnosed with anal fissures who presented to our clinic between 2017 and 2022. SETTING: Single center (University hospital). PATIENTS: A total of 217 patients who met the inclusion criteria were analyzed, with 143 receiving BT alone and 74 receiving the combination of BT + TD. INTERVENTIONS: BT was administered as 100 IU injected into four quadrants. TD was applied twice daily for 10 days immediately following the BT injection. MAIN OUTCOME MEASURES: Primary outcome measures were fissure healing at 2 months and days to pain-free defecation. Secondary outcome measures were complete healing and recurrence rates at 24 months. RESULTS: There were no significant differences in demographic characteristics and symptom duration between the BT and BT + TD groups. The median time to pain-free defecation was 7 days across the entire series, with no statistical difference between groups. At 2 months, complete healing was observed in 74.4% of patients, with no significant difference between groups: 74.8% for BT and 74.3% for BT + TD. During a median follow-up of 53 (22-101) months, a recurrence rate of 26.3% was observed, and TD showed no effect on complete healing and recurrence rates. LIMITATIONS: The most significant limitation of our study is its retrospective design and the absence of a placebo control for TD. CONCLUSION: The study demonstrates that BT is an effective and safe treatment for CAF, with or without the addition of TD. The combination therapy did not show superior outcomes.