A group of 66 patients with locally advanced T2-T4 NOMO TCC of the bladder were treated with three cycles of neo-adjuvant M-VAC chemotherapy. Of 65 evaluable patients, 18 (28%) were T2, 22 (34%) were T3a, 21 (33%) were T3b, and 4 (6%) were T4a. Patients were restaged clinically by repeat CT scan and TURB and were to undergo pathologic staging. Partial cystectomy was to be performed in patients with initial monofocal lesions who responded to therapy. As the study evolved, many patients who responded to M-VAC underwent clinical restaging only. Clinical response incorporated the results of the CT scan, cytology, and TURB. The overall clinical response rate was 82%. A cCr was attained in 28 of the 65 (43%) patients, and 25 of the 65 (38%) patients attained a cPR; 7 patients (11%) had stable disease, and 5 (8%) had progression. The median follow-up is 36(+) months (6(+)-78(+) months). The overall survival for all patients is 82% at 2 years, and 3 year survival is 73%. Of 65 patients, 44 (68%) were managed with conservative therapy (TURB or partial cystectomy). Of 44, 34 (77%) are alive, 28 (64%) with a functional bladder. Patients who had downstaging of their tumors to absence of disease (TO) or superficial disease have 2 and 3 year survival of 86 and 83%. For patients with muscle-infiltrating tumors after M-VAC, 2 and 3 year survival is 89 and 32%. Of 65 patients treated in this study, 28 (43%) have conserved normal bladder function. Response to chemotherapy may be the most important predictor of survival. Although bladder conservation is feasible in selected patients, they remain at risk for recurrence.