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Rituximab (RTX) is an effective therapy for patients with pemphigus; however, the therapy does not prevent relapse.To compare early relapsing patients (before 12 months) and late relapsing patients (after 24 months) following RTX therapy.In this prospective study, 19 patients were enrolled (14 with pemphigus vulgaris and 5 with pemphigus foliaceus). The baseline disease score, autoantibody levels, and percentage of CD20+ cells of patients with pemphigus were measured. Patients received 1 cycle of RTX and were followed for 26 months.Among early relapsing patients (n = 5), the time to relapse was 6 to 11 months. Among late relapsing patients (n = 6), the time to relapse was 24 to 26 months. A significant difference was observed in the mean baseline anti–desmoglein 1 (DSG1) index between early relapsing (705.72) and late relapsing patients (210.4) (P = .0014). A significant negative correlation was found between the baseline anti-DSG1 index and time to relapse (r = −0.777, P = .00009).The small number of patients with pemphigus foliaceus.Because patients with high baseline anti-DSG1 indices relapsed earlier, it may be important to follow these patients closely for the initial 12 months after RTX therapy. These patients may require a maintenance RTX dose during the first 12 months after RTX therapy.