Aim: To present our clinical experience about infective complications due to ultrasound guided transrectal prostate biopsy under ciprofloxacin plus third-generation cephalosporin (Ceftriaxone) combination prophylaxis. Material and Method: The 1193 patients that used combination of ceftriaxone 1 g intramuscular 1 hour before biopsy and ciprofloxacin 500 mg twice a day for 5 days after biopsy were included to study. Before biopsy, urine analysis and urinary cultures were not performed routinely. Serious infective complications such as acute prostatitis and urosepsis, causing microorganisms were evaluated. Results: Serious infective complications occurred in (1.3%) 16 patients. Fifteen of them had acute prostatitis and urine culture results were positive in 10/15 patients for Escherichia coli. The strains were uniformly resistant to ciprofloxacin. Only 1 patient had urosepsis and his blood and urine cultures demonstrated extended-spectrum beta-lactamase-producing (ESBL) Escherichia coli also resistant to ciprofloxacin. Antibiotic treatment-related side effects were not observed in any patient. Discussion: Although there is not a certain procedure, ciprofloxacin is the most common used antibiotic for transrectal prostate biopsy prophylaxis. On the other hand, the incidence of ciprofloxacin resistant Escherichia coli strain is increasing. Thus, new prophylaxis strategies have to be discussed. Ceftriaxone plus ciprofloxacin prophylaxis is safe and can be useable option for prophylaxis of prostate biopsy.