Transrectal ultrasound-guided core prostate biopsy is a key event in the diagnosis of prostate cancer, transient side events such as local pain, haematuria, haematospermia, dysuria, and rectal bleeding are reported in a large number of patients. Antimicrobial agents lower the incidence of postbiopsy infectious complications. The timing and duration of the regimen and the route of administration remain controversial. We developed a standard prophylactic regimen, in which safety and efficiency were maximized, while costs and variability were minimized. Accordingly we prospectively evaluated 425 consecutive patients, who underwent outpatient transrectal ultrasound-guided prostate biopsy after a single dose versus three doses of levofloxacin.