OBJECTIVES: Gemcitabine and cisplatin (GC) is an active combination in the treatment of metastatic bladder cancer. We have prospectively analyzed the efficacy and tolerability of GC as neoadjuvant treatment of invasive bladder cancer MATERIALS AND METHODS: In this single-institution phase II trial, patients with muscle-invasive transitional cell carcinoma received three cycles of gemcitabine 1200 mg/m² on days 1 and 8 with cisplatin 75 mg/m² on day 1 prior to surgery. Radiologic response was evaluated by computed tomography and magnetic resonance imaging. All patients were referred to surgery after chemotherapy completion RESULTS: Between June 2002 and March 2005, 22 patients (19 males) were enrolled. Median age was 63 years. Initial stage was II (T2) in 11 and III (T3-4) in 11 patients. Median follow-up is 26 months (4-43). Partial or complete radiologic response rate was documented in 13 out of 20 assessable patients (70%). One patient was excluded due to sarcomatoid carcinoma at definitive pathologic examination. Cystectomy was performed in 15 patients and pelvic radiotherapy in four patients. Nine out of 21 patients (43%) relapsed and four (19%) died due to disease progression. Complete pathologic response was observed in four patients (26.7% of 15). Median progression-free survival was 27 months (CI 95% not reached) with median overall survival of 36 months (CI 95%: 28.7 - 43.3). Grade III/IV toxicity was infrequent, with no deaths due to chemotherapy CONCLUSIONS: The combination of GC is effective and well-tolerated when used as neoadjuvant therapy in muscle-invasive bladder cancer. Longer follow-up is necessary to evaluate its impact on the overall survival of these patients.