We evaluated the complications of transrectal and transperineal ultrasound-guided prostatic biopsy in 280 patients. All patients underwent antibiotic prophylaxis with a different scheme according to the approach for the biopsy. Urine culture and, in some patients, blood culture have been collected after biopsy. We have reported the same rate of complications for the two modalities except for a lower rate of positive urine culture and blood culture in the group of patients submitted to transperineal biopsy; this type of approach, then, should be considered of first choice in some patients with a higher risk of infections.