For diagnosis of prostate cancer, prostate biopsy accompanied by TRUS is the current method applied today.The aim of this study was to compare targeted antibiotic prophylaxis, chosen according to rectal swab results before the procedure, with routinely administered prophylaxis and to investigate the effect on infective complications.The study included 140 patients with 12-quadrant prostate biopsy accompanied by TRUS in our hospital from 2018 to 2020. The first group had antibiotherapy prophylaxis administered according to the results of rectal swabs before the procedure. The second group had routine ciprofloxacin prophylaxis administered. Patients were followed prospectively for 1 month after the procedure.When the mean age, systemic diseases and distribution in both groups are examined, there was no significant difference observed. Fever (> 38.5 °C) was observed in 3 patients in the rectal swab group (4.3%), while it was identified in 10 people in the control group (14.1%) (p = 0.047). Major complications were observed in 3 people in the rectal swab group (4.3%) and in 7 people in the control group (9.9%) (p = 0.012).The results of the study identified that routine administration of targeted antibiotic prophylaxis may be more effective in preventing infective complications compared to standard prophylaxis. Targeted prophylaxis is recommended for risky patients in the guidelines. However, the lack of difference between the groups in terms of age and comorbidities supports the need to administer targeted prophylaxis not just to risky patients but as well as routine practice.