Background: Pemphigus vulgaris (PV) is an autoimmune bullous disorder that is fatal if left untreated. High dose systemic corticosteroids are the basis of therapy. The addition of immunosuppressive agents has improved the disease outcome and reduced the required corticosteroid dose and related toxicity. Mycophenolate mofetil is increasingly used as a steroid-sparing agent in immunotherapy of PV. Herein, we tried to appraise the efficacy of mycophenolate mofetil and topical clobetasol in the control of the major relapses of pemphigus vulgaris. Method: Seventeen patients with severe relapse of pemphigus vulgaris were included in this study. All patients had complete remission on/off therapy before this period of recurrence. The patients were treated with 2g/day mycophenolate mofetil and 25-35g/day topical clobetasol propionate ointment. All patients were monitored for the side effects of therapy. Result: The patients were followed for a mean period of 12.7 months. The average length of time from initiating mycophenolate to 50% control (partial remission), which occurred in all patients, was 6±1.17 weeks. Fifteen patients achieved complete remission averagely at week 20.8±7.70. The average duration of followup after complete disease control was 8 months (ranging from 2-13.5 months). Three patients were free of lesions for more than 12 months and 10 for more than 6 months. No important mycophenolate mofetil related complication was observed during treatment. Conclusion: The combination of mycophenolate mofetil and topical corticosteroid can be used to control PV relapses and taper-off corticosteroid.