A prospective, randomized trial in which 236 patients received oral levofloxacin, either at 600 mg/day for 1 day (n = 124) or 300 mg/day for 3 days (n = 112). Urinalysis, plasma white blood cell count (WBC) (per mm3), and C reactive protein (CRP) (mg/dl) levels were checked before prostate biopsy (PBX), on the day after PBX, and on the seventh day after PBX. Two patients (1.61%) who received 600 mg for 1 day and 2 patients (1.79%) who received 300 mg for 3 days had febrile infectious complications. There was no statistically significant difference between levofloxacin at 600 mg for 1 day and levofloxacin at 300 mg for 3 days regarding the elevation of WBC and CRP. We can perform PBX safely with levofloxacin at 600 mg for 1 day as prophylaxis and recommend this method from the point of view of the decrease of antibiotic-resistant strains.