OBJECTIVE We retrospectively evaluated the efficacy and toxicity of modified M-VAC therapy for locally advanced or metastatic urothelial carcinoma. METHODS From 1993 October to 2005 February, 28 patients were treated with modified M-VAC therapy and 25 of 28 patients had lesions suitable for the evaluation. The modified regimen was the combination of methotrexate at a dose of 30 mg/m2 on day 1, vinblastine at a dose of 3 mg/m2 on day 2, doxorubicin at a dose of 30 mg/m2 on day 2, and cisplatin at a dose of 70 mg/m2 on day 2 with courses repeated every three weeks. RESULTS The median number of cycle was 3 (1 to approximately 7 cycles). Six of 25 patients achieved complete response (CR) and six partial response (PR), resulting in a 48% response rate. With a median followup time of 65.6 months, the median survival was 9.3 months and the 1-year and 2-year survival rates were 33.5% and 9.6%, respectively. The median progression-free survival was 6.0 months. Grade 3 and 4 toxicities included neutropenia (84.4%), thrombocytopenia (40%), anemia (56%), febrile neutropenia (20%), nausea, vomiting (8%). CONCLUSIONS Although response rate of modified M-VAC therapy was similar to classic M-VAC therapy, but modified M-VAC therapy had shorter response duration and more frequent toxicities. We were not able to find the benefits of modified M-VAC therapy.