Background <p>Globally, infective complications following TRUS-guided biopsies along with emerging fluoroquinolone-resistant bacterial strains are a growing concern. Lack of specific guidelines on this subject necessitates the need to explore potential strategies to prevent such complications. Intra-prostatic antibiotic administered during TRUS is evaluated as an effective strategy to minimize infections with minimal systemic adverse effects.</p> Objective <p>To compare the efficacy of Augmented Prophylaxis using combined single dose intra-prostatic antibiotic injection and oral prophylactic antibiotic with standard oral prophylactic antibiotic to prevent urinary tract infections(UTI) and its associated complications in patients undergoing TRUS Guided Prostatic Biopsy.</p> Methods <p>We have included one hundred and ninety consecutive consenting patients for TRUS guided prostate biopsy for diagnosis of prostate cancer between July 2021 and January 2024, they were randomized into 2 groups—first group, receiving intra-prostatic injection of amikacin with oral ciprofloxacin (group ‘T’) and second group receiving only oral ciprofloxacin (group ‘C’). The incidence of urinary tract infections and associated complications during a 7-day follow-up was assessed among the two groups.</p> Results <p>Ninety-five patients were assigned to each of the groups ‘T’ and ‘C.’ We observed that there were statistically significantly lower UTI rates in group ‘T’ compared to group ‘C’ (1.25 vs 12.63%, <i>p</i> = 0.002). Additionally, Group ‘T’ exhibited A lower incidence of post-biopsy complications like sepsis and LUTS.</p> Conclusion <p>Intra-prostatic antibiotic is an effective adjunct to Oral antibiotic as a prophylaxis to prevent post-TURS urinary tract infectious complications.</p>