Temafloxacin is a new fluoroquinolone that achieves a high urine concentration and has potent, broad-spectrum antimicrobial activity against most pathogens associated with urinary tract infections. The clinical efficacy and safety of temafloxacin were assessed in adult females with acute, uncomplicated urinary tract infection in a series of three randomized, double-blind trials. A total of 555 clinically evaluable females of 919 enrolled from 75 centers received temafloxacin 200 or 400 mg once daily for 3 or 7 days, or a control regimen. The latter consisted of trimethoprim/sulfamethoxazole 160 mg/800 mg, ciprofloxacin 250 mg, or norfloxacin 400 mg, each given twice daily for 7-10 days. Clinical cure or improvement occurred in 305 of 308 temafloxacin patients (99%) and in 247 of 247 controls (100%). Corresponding bacterial eradication rates were 99% (289/292) and 96.7% (237/245), respectively. The most frequently observed adverse events were nausea (3.5% of the temafloxacin group, 6.5% of the reference quinolone group, and 6.6% of the trimethoprim/sulfamethoxazole group) and headache (5.4%, 3.7%, and 3.1% of the same respective groups). These results demonstrate the clinical efficacy and safety of temafloxacin, given once daily, in a large number of females with acute, uncomplicated urinary tract infection.