We reviewed and analyzed the most effective methods to reduce infectious complications (IC) after transrectal prostate biopsy (TRPB). We included only prospective randomized-controlled trials in the analysis. The analysis neither demonstrated any superiority of fluoroquinolones over other antibiotic classes nor of targeted antibiotics over empiric regimens in men undergoing TRPB. However, longer course antibiotics (3 days or more) compared to single dose or day regimens, combination of fluoroquinolones with aminoglycosides compared to fluoroquinolones alone and povidone-iodine rectal cleansing compared to control significantly reduced IC following TRPB. A combination of addition of aminoglycosides to oral antibiotics for 3 days along with povidone-iodine rectal cleansing may be an optimum strategy to minimize the risk of IC after TRPB.