Background: Pemphigus is a group of potentially fatal autoimmune mucocutaneous blistering diseases. Rituximab (RTX) is a chimeric anti‑CD20 monoclonal antibody being increasingly used and becoming the first‑line therapy in the management of pemphigus.Aim: To evaluate the efficacy and safety of rituximab in patients of pemphigus vulgaris (PV) who either did not respond or relapsed after conventional therapeutic regimens and in treatment naive pemphigus patients. Methods: The study included pemphigus patients coming to the tertiary health care centre, Jaipur between January 2020 and December 2022. All enrolled patients received two doses of rituximab (1 gram in each) as intravenous infusions two weeks apart as per the rheumatoid arthritis protocol. The efficacy and safety were evaluated by assessing pemphigus area and activity score (PAAS) before and after the therapy, clinical response and any adverse events during follow‑up. Results:Twenty Two (fifteen males and seven females) patients were included in the study. The age of these patients ranged from 27 to 60 years, with a mean of 43.8 ± 9.8 years. There were 21 (95.45%) patients with PV (20 mucocutaneous type and 01 mucosal) and 1 (4.6%) with pemphigus foliaceus. Among these patients, 15 (56.25%) were relapse cases, 4 (25%) were non‑responders, and 3 (18.75%) were fresh cases who received rituximab as first‑line therapy. Fourteen (87.5%) patients reached complete remission off therapy over a median time of 6.36 months. Rituximab was well‑tolerated by our patients, and no serious adverse events were observed. Conclusion: Rituximab had demonstrated a robust and long-lasting response in individuals with PV following a single course and has an excellent safety and tolerability profile.