5'-Deoxy-5-fluorouridine (5'-DFUR), an oral fluorinated pyrimidine carbamate, is widely used in patients with gastrointestinal and breast cancers because of its effectiveness. However, in bladder cancer, response rates have only been reported in Phase II clinical trials. Therefore, we conducted a prospective randomized trial to investigate chemoprophylactic effect of 5'-DFUR against recurrence of superficial bladder cancer after transurethral bladder tumor resection (TUR-Bt). The subjects were grouped as follows: 1) 5'-DFUR group (n = 31), received 600 mg/day of 5'-DFUR starting 2-3 weeks after TUR-Bt for 2 years; and 2) control group (n = 31) received no 5'-DFUR. Although there was no significant difference between groups, the cumulative recurrence rates was more favorable in the 5'-DFUR group (p = 0.256) than in the controls. Results according to cancer factors showed that, in patients with G2 based on grading, those in the 5'-DFUR group tended to have a lower recurrence rate than the control group (p = 0.070). There was a 40% incidence of adverse drug reactions (12/30 patients), primarily slight gastrointestinal symptoms which disappeared or improved with drug discontinuation. The results of the present study suggest that 5'-DFUR might be the choice of treatment to prevent recurrence of superficial bladder cancer.