Background: Eye disease due to Herpes simplex virus (HSV) commonly presents as epithelial keratitis which, though usually self-limiting, may persist or progress without treatment. It is a highly prevalent and visually disabling disease in both pediatric and adult populations. Aims: To compare efficacy of ganciclovir & acyclovir in the treatment of Herpes simplex epithelial keratitis. Methods: This randomized controlled trial was carried out in the Department of Community Ophthalmology BSMMU, Dhaka and Ispahani Islamia Eye Institute and Hospital, Dhaka, from October 2019 to February 2021. A total of 38 patients with Herpes simplex keratitis attending outdoor were included in this study. Clinically diagnosed by ophthalmologist, dendritic keratitis or geographic keratitis patients age belonged to 19 - 65 years of both gender were enrolled The patients were divided into two groups by randomizations to either receiving ganciclovir gel 0.15% considered as group I (n=19) or acyclovir 3.0% ointment considered as group II (n=19) by using the lottery method The patients were followed up at days 2, 7, 14 and 21. Results: The mean ulcer size at day 7 were 0.92±0.96 (mm) in group I and 2.28±1.46 (mm) in group II and at day 14 were 0.09±0.41 (mm) in group I and 0.68 ±0.27 (mm) in group II. The difference was statistically significant (p<0.05) between the two groups. Conclusion: Ganciclovir 0.15% ophthalmic gel and acyclovir 3% ophthalmic ointment were found equally effective in their ability to heal herpes-induced keratitis in the patients.