Background: Vernal keratoconjunctivitis (VKC) is an acute on – chronic inflammatory disease of the conjunctiva and cornea,1,2 encountered usually in the first decade of life in children. Aims & Objectives: To determine the efficacy and safety of Tacrolimus skin cream in the resolution of moderate to severe Vernal Keratoconjuctivitis (VKC). Material and Methods: A prospective clinical trial was conducted at the Ophthalmology department of Ramkaran Joshi Hospital, Dausa, Rajasthan, from Sep 2019 – Aug 2020. In this study, 54 consecutive cases (108 eyes) with moderate to severe VKC, betweenthe ages of 4 – 18 (mean 7 years) years were included. There were 13 newly diagnosed cases and 41 recurrent. After discontinuing their previous medications, they were treated with Tacrolimus skin cream, 0.03% applied into the lower conjunctival fornix twice a day along with lubricants for a period of 4 –8 months. Clinical signs and symptoms were recorded at the beginning of the treatment and at all follow-ups which were conducted weekly for one month and then every month for one year. Results: The duration of therapy was 4 – 8 months (mean 6 months). The patients were followed-up for a mean duration 10 ± 1.5 months. There was marked subjective as well as objective improvement in all cases within onemonth of therapy. There was no need for any additional therapy. No toxic effects of Tacrolimus were observed in any case. Conclusion: It can be concluded that Tacrolimus skin cream (0.03%) is an effective therapy for moderate to severe cases of vernal keratoconjuctivitis. It acts as a safe alternative to topical steroids.