BACKGROUND Infection is an important complication that may follow transrectal biopsy of the prostate. Empirical rather than targeted antibiotic prophylaxis with fluoroquinolone is usually given to prevent infective complications. This practice is due to paucity of local studies comparing the use of empirical and targeted prophylactic antibiotics. The aim of this study was to compare empirical and targeted prophylactic antibiotics in patients who had prostate biopsy in Lagos State University Teaching Hospital, Ikeja (LASUTH). MATERIALS AND METHODS A prospective randomized study was conducted between January 2015 and December 2015 at the Lagos State University Teaching Hospital. All the patients who met the inclusion criteria for transrectal ultrasound guided prostate biopsy were recruited and they all had urinalysis, urine M/C/S and rectal swab for M/C/S prior to the procedure. They were all then randomized into two equal groups; Targeted antibiotic group (A) and Empirical antibiotic group (B). Group A had prophylactic antibiotic according to rectal swab result while group B had parenteral Ciprofloxacin and Metronidazole. They all then had transrectal ultrasound guided prostate biopsy under caudal anaesthesia .They were discharged home after the procedure and were seen weekly for four weeks. Proforma designed for the study was used to gather patients’ biodata record, test results and complications. Data were entered and analyzed using the statistical Package for Social Sciences (SPSS) IBM Version 19. Percentages, mean and standard deviation of numerical tables were determined. Chisquare or Fischer’ exact tests were used to compare categorical variables as the case may be, while student ‘t’ test was used to compare means of numerical variables. For all statistical tests, confidence interval was set at 95% and statistical tests were considered significant if P<0.05. Microsoft excel was used to draw charts. RESULTS One hundred patients who fulfilled the inclusion criteria were studied. The overall urinary tract infection complication rate was 12%, one patient in the targeted group (2%) and five patients in the empirical group (10%). Fluoroquinolone resistant organisms were responsible for infection in all the six patients. Two of the patients in the empirical group had urosepsis and had to be admitted while none of the patients in the targeted group was admitted for infective complications. CONCLUSION Targeted antibiotic prophylaxis was associated with a decrease in infective complications in patients undergoing prostate biopsy for the diagnosis of carcinoma of the prostate compared to empirical antibiotic prophylaxis, but it was not statistically significant.