We clinically evaluated the efficacy of neoadjuvant M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) therapy followed by radical cystectomy. A total of 21 patients with locally invasive bladder cancer received neoadjuvant M-VAC therapy with an average of 2.4 courses (range 2-4). Of the 21 patients, 4 had stage T2N0M0, 11 had stage T3aN0M0, 5 had stage T3bN0M0 and 1 had stage T4N0M0 at diagnosis. Of the 21 patients, 3 had clinically complete responses (cCR) and 12 had partial responses (cPR), for an overall response rate of 71.4%. The patients who responded to the chemotherapy (cCR + cPR) had a 2-year disease free rate of 80.0% in contrast to 50.0% for the remaining patients who did not respond. A pathological response (pT0, pT1) was achieved in 6 (28.6%) of the 21 patients. The 5 patients in this group remain free of disease for 15 to 79 months (mean 58.8 months). These preliminary results suggest that the patients who achieve either a complete or partial response, in particular those had pathological stage of pT0 or pT1, may have a favorable clinical course.