Abstract: Alopecia areata is a chronic disease that may respond poorly to treatment. This study aimed to examine the efficacy of methotrexate plus prednisolone in severe alopecia areata. A total of 10 patients with long-lasting extensive alopecia areata were studied. These patients were recruited from two private dermatological clinics in Tehran (Iran) from September 2011 through December 2012. Oral prednisolone (initial: 0.5 mg kg day-1) and oral methotrexate (5-10 mg week-1) were administered and tapered when a full hair regrowth was achieved. A total regrowth of the terminal hair was regarded “success”. Descriptive analysis was used in this study. Success was achieved in 80% of the patients. Within a mean follow-up of 14.40 months after treatment, relapse occurred in 4 patients (patchy loss = 2, patchy and succeeding diffuse loss = 1, diffuse loss = 1). Relapse resolved using local corticosteroid/dose increase in all 4 patients. Complications were minor and resolved spontaneously. This study showed that oral methotrexate plus oral prednisolone is effective and safe in severe alopecia areata.