BACKGROUND : Pemphigus Vulgaris (PV) is a vesiculobullous autoimmune disorder characterized by production of autoantibody against cellular adhesion molecules. The treatment of PV is based on the use of systemic corticosteroid along with immunosuppressive therapy, but sometimes there are limited resistant lesions not responding to conventional systemic therapy. This double-blind, randomized clinical trial was designed to evaluate the efficacy of intralesional rituximab versus triamcinolone in treatment of the refractory scalp and mucosal pemphigus lesions. METHODS : 2 refractory lesions of PV were selected in 21 patients, and they were randomly assigned to two groups to be treated with either intralesional triamcinolone or rituximab for 2 times at one-month interval. All of the patients were under treatment with prednisolone and azathioprine. Patients were visited at the baseline, 1 and 6 months after treatment, and all information including demographic characteristics of the patients, Pemphigus Vulgaris Lesion Severity Score (PVLSS), Epithelialization Index (EI) and patient's satisfaction (using Visual Analogue Scale (VAS)) were obtained. The collected data were analyzed using SPSS software (ver18). RESULTS : The results showed that, both rituximab and triamcinolone were effective in treatment of the refractory PV lesions (p < 0.05). However, there was no significant difference between the effect of intralesional rituximab and triamcinolone (p > 0.05). In addition, no side effect was observed in both groups. CONCLUSIONS : Regarding the results of the present study, the use of intralesional rituximab can be suggested for treatment of the resistant PV lesions as an alternative to intralesional triamcinolone or using more aggressive systemic therapy.