Background: Recently, rituximab has been successfully used for the treatment of pemphigus family, the main subtype of which is pemphigus vulgaris (PV). The aim of this study was to determine the efficacy and safety of rituximab in refractory PV. Methods: In an observational study extending from November 2014 to February 2016, 30 patients with refractory PV were treated with rituximab. Response to therapy, duration of clinical remission, relapse rate, serology, and side effects of treatment with rituximab were evaluated. Results: At the end of the follow-up with a mean duration of 7.6 (6-14) months, 25 (83.3%) patients achieved complete remission with or without systemic therapy. The mean duration of disease control was 2.8 months. In all patients, the serum levels of antidesmoglein 1 and 3 IgG antibodies were reduced after rituximab therapy. In 23.4% of the patients, a clinical relapse occurred at a mean of 9.6 months following the initiation of the treatment. Infusion-related reactions occurred in 18 (60%) patients. The lack of a control group, concomitant use of corticosteroid and immunosuppressive agents, and a limited follow-up period were among the limitations of our research. Conclusions: Rituximab is a good treatment modality for refractory PV, which extends the mean time to relapse in patients. To further extend our knowledge on the efficacy and safety of rituximab therapy, more randomized controlled trials with larger sample sizes and prolonged follow-up durations are required.