To assess the safety and to obtain preliminary data on the efficacy of the three-drug combination chemotherapy with gemcitabine, oxaliplatin and vinorelbine in patients with metastatic bladder cancer. Patients with metastatic or locally unresectable advanced bladder cancer who had received either no or one previous systemic chemotherapy regimen were eligible. All patients received intravenous gemcitabine 700 mg/m(2) and vinorelbine 25 mg/m(2) on day 1, then intravenous oxaliplatin 85 mg/m(2) on day 2, every 14 days. Fifteen patients were enrolled. Twelve patients were unfit for cisplatin. A median of five cycles per patient were delivered. The most common toxicities were neutropenia, nausea and vomiting, mucositis and diarrhoea. Two complete responses and one partial response were observed for an overall response rate of 23%. Median progression-free survival was 5.7 months and overall survival was 8.6 months. Although active and tolerable, the described three-drug combination chemotherapy showed no obvious incremental increase in efficacy compared with two-drug regimens. Further clinical trials are not recommended.