Abstract Background To compare the efficacy and safety of rituximab (RTX), calcineurin inhibitor (CNI) and cyclophosphamide (CTX) plus glucocorticoids in the treatment of primary membranous nephropathy (PMN). Methods Totally 478 biopsy-proven PMN patients in single center were retrospectively included. After 1:1 propensity score matching (PSM), 258 patients were included in RTX, CNI or CTX group (86 patients in each group). Results After PSM, there were no differences on serum creatinine, eGFR, serum albumin, urine protein, anti-PLA2R antibody levels among groups. The follow-up duration was 12 (10.5, 18) months in CNI group, 12 (12, 18) months in CTX group and 12 (12, 18) months in RTX group. Throughout entire follow-up period, 39 patients (45.3%) in CNI group, 47 patients (54.7%) in CTX group, and 59 patients (68.6%) in RTX group achieved total remission (TR, either complete remission or partial remission). The survival curve showed a higher rate of TR in RTX group than CNI group (p = 0.018). A relapse occurred in 15 of 39 (38.5%) patients in CNI group, significantly higher than CTX group (4.3%, p