Prolonged infusion of low-dose gemcitabine and cisplatin (GC) proved to be an effective treatment for patients with advanced bladder cancer. One hundred and twenty untreated patients with stage III/IV bladder cancer were randomized to receive either gemcitabine (250 mg/m(2)) 6-h infusion on days 1 and 8, and cisplatin (70 mg/m(2)) on day 2 every 21-day cycle (arm 1) or gemcitabine (1,250 mg/m(2)) 30-min infusion on days 1 and 8, with the same dose of cisplatin (arm 2). The 92 males and 28 females included in the study had a median age of 62 years (range 40-85 years). Among the 120 patient, complete response was achieved in 11.7 % (7/60 patients of arm 1) and 5 % (3/60 patients of arm 2). Eighteen patients in arm 1 (30 %) and 17 patients (28.3 %) in arm 2 had partial response on therapy. Thus, the overall response rate of patients in arm 1 and arm 2 was 41.7 % (25/60 patients) and 33.3 % (20/60 patients), respectively (p = 0.37). No significant difference in median time to disease progression (26 vs. 24 months, p = 0.4), median survival (12 vs. 16 months, p = 0.8), and 1-year survival (49.9 vs. 54.7 %, p = 0.8) was detected between arms 1 and 2, respectively. Main toxicities were similar in both arms with no statistically significant differences. Low-dose, prolonged infusion gemcitabine in combination with cisplatin is not inferior to the standard GC regimen with favorable toxicity profile and less financial costs.