Systemic cisplatin-based chemotherapy regimens are the gold standard in advanced bladder cancer. Gemcitabine plus cisplatin (GC) therapy has often been used, although there is no significant evidence that it is better than methotrexate, vinblastine, adriamycin, and cisplatin (MVAC) therapy in neoadjuvant chemotherapy. We retrospectively evaluated the relative efficacy of the two chemotherapeutic regimens in the management of muscle-invasive bladder cancer on patients who had had radical cystectomy for clinical stage T2-T4, N and, M0 bladder cancer. Fourteen patients (24.1%) and 44 (75.9%) patients were treated with GC and MVAC therapy, respectively. GC therapy was significantly more effective than MVAC therapy in pathological down-staging (to pT0) rate. On multivariate analysis, the choice of regimen (MVAC) was an independent predictor of the presence of residual cancer after a neoadjuvant chemotherapy. The clinical response to neoadjuvant GC therapy was superior to that to neoadjuvant MVAC therapy. Moreover, GC therapy was associated with less non-hematologic toxicity than MVAC therapy, especially with respect to the occurrence of nausea.