Background: Cisplatin-based chemotherapy is the mainstay of the treatment for advanced urothelial cancer, but patients with renal insufficiency before therapy are usually contraindicated to receiving platinum-based chemotherapy. Paclitaxel is one of the most promising agents against advanced urothelial carcinoma in recent trials and it can be easily tolerated even in patients with compromised renal function. We conducted a study in order to evaluate the efficacy and safety of paclitaxel as a first-line therapy in advanced urothelial carcinoma patients. Methods: Thirteen advanced chemo-naive urothelial carcinoma patients with a median age of 71 years were studied, seven of them demonstrating renal insufficiency (pretreatment serum creatinine ≥1.5 mg/dl). All 13 patients received a minimum of two cycles of paclitaxel 175 mg/m2, delivered by intravenous infusion for 3 h every 3 weeks. Results: Four of the 13 patients responded to treatment, a response rate of 30.8%, with two of these achieving complete remission and two showing partial responses. The median overall survival period of all 13 patients was nine months (95% CI: 6.51-11.49) and our study revealed a statistical tendency in the difference of median overall survival time between responders and non-responders (13 months versus 7.5 months, log-rank p = 0.038), although the number of cases was limited. The differences in response rate and median overall survival time, comparing patients with renal insufficiency and those with normal renal function, were not significant. Treatment-related toxicity was mild, with only two (15.4%) patients suffering from grade 3-4 leukopenia. No treatment-related mortality was noted. Conclusions: Single-agent paclitaxel can be used as a first-line therapy in advanced urothelial carcinoma patients, and is especially suitable for those with pretreatment renal insufficiency, since the antitumor activity is significant while toxicity is well tolerated.