This study explored the real terms value of rectal swab testing and targeted antibiotic prophylaxis in patients undergoing transrectal ultrasound prostate biopsy in view of increasing bacterial resistance to fluoroquinolones (17.6% in North America, 40% in Hong Kong). The authors retrospectively analysed infectious complications from the procedure in 244 patients who received targeted antibiotic prophylaxis (TAP) based on rectal swabs prior to biopsy. This was compared to 264 consecutive patients who did not receive TAP in the period prior to introduction of the rectal swab protocol. Those who had ciprofloxacin-resistant organisms on their rectal swab received ceftriaxone, gentamicin or aztreonam depending on sensitivities compared with standard ciprofloxacin, co-trimoxazole or co-amoxiclav. Infectious complications were defined as requiring hospital admission, emergency room visit or additional treatment with antibiotics. Infectious complication rate in the TAP group was 1/244 (0.41%) compared to 7/264 (2.65%) in the pre-TAP group (p≤0.05). Taking into account hospital bed days required to treat the complications encountered and the cost of carrying out rectal swabs, a real term saving of $19,076.88 was demonstrated. Although the numbers in this study are small, it adds to the growing body of evidence on the value of TAP in day-to-day practice.