To assess the efficacy and safety of a single-dose therapy for acute uncomplicated cystitis (AUC), we compared 4 treatment regimens in 120 women. Patients eligible for the study were randomly assigned to one of four treatment groups: Ciprofloxacin (CPFX) 200 mg in a single oral dose (group A); 200 mg once daily for 3 days (group B); 200 mg twice daily for 3 day (group C); and cefpodoxime-proxcetil (CPDX-PR) 200 mg once daily for 3 days (group D). The efficacy was evaluated 3 days after the single-dose therapy or at the end of a three-day therapy according to the criteria proposed by the Japanese UTI Committee. The overall clinical efficacy in a total of 107 patients was evaluated to be excellent, moderate, and poor in 72 (67.3%), 35 (31.8%), and 1 (0.9%), respectively. The causative organisms were eradicated in 88.0, 85.2, 85.2, and 82.1% of the patients in groups A, B, C, and D, respectively. Recurrence was identified in 3 (2 in group A and one in group D) of 16 patients who were followed at 2 to 3 weeks after the treatment. No adverse reactions related to the antibiotics were recognized in the study. There were no significant differences in the clinical efficacy or recurrence rate among these four treatment regimens. These results indicate that the single-dose therapy of CPFX is the treatment of choice in women with AUC.