|Abstract||Purpose: Rectal culture screening for fluoroquinolone (FQ)-resistant Enterobacteriaceae before transrectal ultrasound guided prostate (TRUSPB) biopsy and targeted antibiotic prophylaxis (TAP) may decrease post-TRUSPB infection rates compared to empiric (EAP) regimens. The objective of this study was to evaluate the effectiveness of targeted relative to empiric prophylaxis regimens on rates of infectious complications after TRUSPB and to determine the baseline prevalence of FQ resistance based on prior rectal swabs. Methods: An electronic search within literature databases including EMBASE and Web of Science (all databases) for articles assessing TAP as an approach to TRUSPB prophylaxis was conducted. Quality assessment was performed using the Hoy instrument. Meta-analysis was performed using MetaXL 5.3. Results: From 15 studies (eight retrospective and seven prospective) representing 12,320 participants, infectious complication incidence was 3.4% in EAP and 0.8% in TAP patients. The number needed to treat with TAP to avoid one more infection when compared to the EAP group was 39. Effect sizes were homogeneous. Prevalence of FQ resistance showed low (15%) and high (28%) subgroups, likely due to region of origin (within and outside USA, respectively). Conclusions: Rectal culture prior to TRUSPB and use of TAP adjusts for endemic FQ resistance and is associated with less infectious complications and resulting morbidity when compared to EAP. Overtreatment associated with augmented prophylaxis approaches may be reduced as a result. Further prospective assessment and cost–benefit analyses are required before widespread implementation can be recommended. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature.