Vitiligo is social taboo in the Indian Society. There are various modalities used for the treatment of vitiligo but none of the modalities alone can effectively treat vitiligo. The aim of the study was to compare the efficacy of weekly oral multidrug therapy in vitiligo cases using trimethylepsoralen, corticosteroid and cyclophosphamide. Methods: Total 108 clinically diagnosed vitiligo patients were enrolled and 26 patients missed during the follow up. So, only 82 patients were included in the study were divided into 2 groups depending on the treatment modalities which includes modality I treated with oral methyleprednisolone (64 mg), oral cyclophosphamide (200 mg), and oral trimethylepsoralen (100 mg) one day in a week after breakfast and were advised to expose all the lesions to sunlight daily for at least half an hour, any time of their own convenience and modality II treated with oral trimethylepsoralen (25 mg) daily at morning time after breakfast. After that patients were advised to expose all the lesions of vitiligo to sunlight after 2 hours of intake of trimethylepsoralen for at least half an hour. Evaluation of efficacy was done by measurement of pigment spread in millimetres. Patients were categorized in four grades on the basis of percentage of pigmentation; they gained during 6 months of follow up as excellent response: 75%-100% repigmentation, good response: 50%-75% repigmentation, moderate response: 25%-50% repigmentation, poor response: 0%-25% repigmentation. Results: Patients treated with modality I and II responded best with focal type of vitiligo, female patients, below 30 years of age, unstable vitiligo, lesions on the face and neck. Statistically significant (p-value<0.05) association was observed with lower age group, unstable vitiligo with modality I response. Patients on modality-I showed excellent response in 20% of cases and 60.01% of cases showed more than 50% of repigmentation compared to modality-II showed excellent response in 10% of cases and 32.24% of cases showed more than 50% of repigmentation after 6 month of therapy. Conclusion: Weekly oral pulse therapy by using three drugs trimethylepsoralen, cyclophosphamide and corticosteroids seems to be good options for treatment vitiligo. Response of this therapy is better with minimal side effect as compared to conventional therapy of vitiligo.