Background: There are several medical and surgical interventions for vitiligo but still the search for a definite cure is going on. The first goal of the therapy is to make the disease stable by preventing the appearance of new lesions. Drugs like oral corticosteroids, methotrexate, and azathioprine have been found effective in this phase. Objective: To compare the efficacy of oral corticosteroids, methotrexate, and azathioprine in patients with unstable vitiligo. Materials and Methods: It was a retrospective data analysis of 319 vitiligo patients, out of which 52 patients with unstable vitiligo who have received treatment in the form of 0.5 mg/kg oral corticosteroids on 2 consecutive days per week, 0.3 mg/kg methotrexate per week, and 1 to 1.5 mg/kg azathioprine daily were selected and were evaluated for the effect of drug for 12weeks. Results: There was no statistically significant difference in the appearance of new lesions in all 3 groups; however, methotrexate showed the early effect which plateaus after a few weeks whereas steroids as well as azathioprine showed a gradual and consistent effect. Conclusion: Methotrexate, steroids, and azathioprine all arrest the disease activity in vitiligo. Methotrexate can be used to arrest disease activity in fast-spreading vitiligo. Azathioprine can be used in patients with active vitiligo, wherever steroids are contraindicated.