The objectives of this study were to determine the tolerability of combined use of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) with external beam radiation therapy (EBRT) and to access the efficacy in patients with locally advanced or metastatic bladder cancer. From December 2000 to November 2010, 30 eligible patients were enrolled in this study. After receiving one cycle of MVAC treatment, all patients received EBRT with a half dose of MVAC treatment followed by two more cycles of chemotherapy. A standard fractionation with daily dose of 1.8-2.0 Gy was used, with the total dose up to 60 Gy over 5-6 weeks. The four-field box technique was utilized for radiation fields. Thirteen patients (43%) had complete response and 11 (37%) had partial response, with an overall response rate of 80%. The median overall survival and progression-free survival was 25.5 months and 12.8 months, respectively. In the complete-response patients, median overall survival was 37.1 months. Grade 3 or 4 neutropenia occurred in 25 patients (83%), but there were no severe infections. One patient (3%) had hemorrhagic radiation cystitis. There were no treatment-related deaths. Combined use of MVAC treatment with EBRT is a favorable therapeutic option for patients with advanced or metastatic bladder carcinoma. Given the safety and benefit profile found in this study, appropriate case selection is warranted in the future.