Objective: The present study was conducted to evaluate the safety profile and efficacy of ganciclovir in cases of viral corneal ulcer and to compare it with acyclovir. Material and methods: It was a randomized controlled comparative study undertaken at the Regional Institute of Ophthalmology, Pt BD Sharma PGIMS, Rohtak, Haryana. The patients were divided into two groups of 25 each. Group I received acyclovir 3% ointment and Group II received ganciclovir 0.5% gel. Patients were followed-up weekly for 1 month. Efficacy of the drug was assessed in terms of visual acuity and extent of healing. Safety profile was assessed by development of ocular irritation, blurring of vision and iatrogenic diffuse punctate keratopathy. The observations were analyzed using unpaired and paired ‘t’ test and Chi-square test. Results: By 14th day, 80% ulcers were healed in Group I while 88% were healed in Group II. The best corrected visual acuity after healing was also similar in the two groups (p = 0.730). The safety profile in terms of ocular irritation, blurring of vision and punctate keratopathy of both the drugs was found to be similar. Conclusion: The efficacy and safety profile of both the drugs was similar in the treatment of viral corneal ulcer.