Objective To evaluate the efficacy and safety of obinutuzumab (OBZ) in the treatment of refractory primary membranous nephropathy (pMN). Methods The clinical data of 15 patients with refractory pMN who received OBZ treatment in Department of Nephrology of The First Affiliated Hospital of Naval Medical University between Jan. 2022 and Sep. 2024 were retrospectively analyzed, and they included basic information, relevant laboratory indexes, clinical and immunological outcomes, and adverse events. Results Among the 15 patients with refractory pMN, 14 (93.3%) were phospholipase A2 receptor (PLA2R)-associated membranous nephropathy (10 cases with positive PLA2R by renal biopsy and 4 cases with no recorded PLA2R results by renal biopsy but with positive serum PLA2R antibodies). During the follow-up period, all 15 patients achieved clinical remission, with 4 (26.7%) patients achieving complete remission and 11 (73.3%) patients achieving partial remission. Of the 12 patients with positive serum PLA2R antibodies, 11 patients had continuously positive serum PLA2R antibodies before OBZ treatment, and 9 (81.8%) patients achieved immunological remission after OBZ treatment. All the 15 patients had previously received immunosuppressive therapy, and all of them were classified as refractory pMN, with 7 (46.7%) patients having been treated with cyclophosphamide combined with corticosteroids, 2 (13.3%) patients having been treated with calcineurin inhibitor combined with corticosteroids, 11 (73.3%) patients having received rituximab. During the treatment, 2 (13.3%) cases of adverse events were observed: 1 patient experienced transient liver dysfunction, and the transaminase returned to normal after discontinuing atorvastatin; another patient developed a positive T-cell spot test for Tuberculosis infection during the intertreatment interval and successfully completed the subsequent OBZ treatment and achieved clinical remission after treatment with isoniazid and rifampicin. Conclusion OBZ demonstrates favorable clinical efficacy in the treatment of refractory pMN, with a low incidence of adverse events.