Background: There is an ongoing trend towards perineal prostate biopsies for the detection of prostate cancer. For many reasons the issue of antibiotic prophylaxis in prostate biopsies is becoming more important, especially with quinolone antibiotics being excluded from this indication and an increasing antibiotic resistance. Considering that the perineal biopsy is a sterile procedure, not giving antibiotics for prophylaxis seems to be an alluring approach. Methods: At the General Hospital Leverkusen, transperineal (TP) MRI TRUS fusion biopsies are performed using the Ginsburg Protocol with a template and software-guided approach in general anesthesia. Patients received single dose antibiotics (Ciprofloxacine 500 mg) two hours prior to surgery from Jan 2019 to Aug 2019 (group 1). Starting in Sep 2019, no antibiotics were used for prophylaxis (group 2). Surgical disinfection using Povidone-iodine was performed ahead of every procedure. In this study, postoperative infection rates were assessed. Patients were followed up by telephone interview at least two weeks after biopsy and were asked about the need for postoperative antibiotics to treat regular UTI, fever, prostatitis or for readmission to other hospitals. Results: A total of 180 TP biopsies were performed with a median of 22 cores (min 18, max 28). Out of 115 cases with antibiotic prophylaxis, no patient was readmitted to the hospital due to infection or fever. Group 2 included 65 patients. No one was readmitted with fever or prostatitis. At the time of abstract admission 45 out of 65 patients in this group were followed up by telephone interview. None needed antibiotics and none was readmitted to a hospital elsewhere. Conclusions: The study shows an infection rate of 0 % for perineal prostate biopsies with or without antibiotic prophylaxis. The results argue in favor of perineal prostate biopsies and challenge the dogma of prostate biopsies needing an antibiotic prophylaxis irrespective of the approach. However, a larger prospective multicenter study should be initiated to ensure patient safety.