Aim: To evaluate the efficacy of prednisolone, warfarin, and dipyridamole therapy combined with mizoribine (PWDM) in the treatment of diffuse immunoglobulin A (IgA) nephropathy in comparison with prednisolone, warfarin, and dipyridamole therapy without mizoribine (PWD) and with methylprednisolone pulse therapy (PWD pulse). Methods: We collected data on 61 patients diagnosed with diffuse IgA nephropathy, and these patients were retrospectively divided into three groups without randomization. Group A included 21 patients before 1987 who were treated with PWD for 24 months, group B included 20 patients from 1987 to 1989 who were treated with PWD pulse therapy for 24 months, and group C included 20 patients after 1990 who were treated with PWDM for 24 months. Clinical features and pathological findings in each group were analyzed retrospectively. Results: The time from initiation of therapy in group A, group B, and group C was 8.9 ± 5.2, 8.1 ± 3.9, and 7.7 ± 3.8 years, respectively. At the latest follow-up examination, the mean urinary protein excretion (mg/m<sup>2</sup>/h) was 17 ± 10 in group A, 22 ± 20 in group B, and 6 ± 6 in group C and had decreased significantly in group C as compared with the other groups. The activity index in all three groups was lower at the second biopsy than that at the first biopsy (5.1 ± 0.8 vs. 6.5 ± 2.1 in group A, p < 0.05; 5.6 ± 0.9 vs. 6.6 ± 1.7 in group B, p < 0.01, and 4.5 ± 1.0 vs. 6.8 ± 1.9 in group C, p < 0.01). The chronicity index in groups A and B at second biopsy was higher than at first biopsy (7.3 ± 1.4 vs. 4.8 ± 1.0 in group A, p < 0.01, and 8.1 ± 2.0 vs. 5.3 ± 0.9 in group B, p < 0.01), but was unchanged in group C. At the latest follow-up examination, 1 patient (4.8%) in group A, 3 patients (15%) in group B, and none (0%) in group C had renal insufficiency. Conclusion: These results suggest that PWDM appears to be more effective than PWD or PWD pulse in ameliorating proteinuria and histological severity of patients with IgA nephropathy.