OBJECTIVES: Rectal culture-guided antibiotic prophylaxis is an effective strategy in preventing post-TRUSBx infections. This study aimed to examine the cost-effectiveness of pre-biopsy rectal swab culture-guided antibiotic prophylaxis in patients undergoing TRUSBx from the societal perspective in Hong Kong. METHODS: A decision tree model was designed to compare clinical outcomes and cost of TRUSBx with rectal culture-guided versus empirical antibiotic prophylaxis in a hypothetical cohort of male patients. Total costs (direct medical cost, indirect cost) and quality-adjusted life-year (QALY) loss for post-biopsy infection care were outcomes of analysis. Model inputs were retrieved from clinical studies published in literature. Sensitivity analysis was conducted to examine robustness of model results. RESULTS: The base-case analysis found rectal culture-guided strategy to be less costly (expected cost HKD1,268 versus HKD1,633) (USD1=HKD7.8) with lower QALY loss (0.00055 QALY vs 0.00084 QALY) when compared to empirical strategy. Sensitivity analysis showed that the total cost of rectal culture-guided arm would become higher than the empirical arm if the effectiveness of rectal culture-guided strategy in reducing post-biopsy infection was less than 12.07%, or if post-biopsy infection rate of empirical strategy was lower than 3.18%. In 10,000 Monte Carlo simulations, rectal culture-guided arm was the preferred option in 98.67% of cases with mean total cost saving of HKD449 per patient (95%CI HKD443–455; p <0.001) and lower mean QALY loss of 0.000335 QALYs per patient (95%CI 0.000332–0.000338 QALYs; p <0.001). CONCLUSIONS: Comparing with empirical antibiotic prophylaxis, the use of rectal swab culture to guide the choice of antibiotic prophylaxis seems to be a cost-saving and effective intervention in men undergoing TRUSBx in Hong Kong.