INTRODUCTION AND OBJECTIVES: A recent populationbased study demonstrated an increasing frequency of infectious complications after prostate biopsy procedures with hospitalization rates approaching 5% (Nguyen et al. J Urol 2010). However it is unclear whether this effect is due solely to bacterial resistance and whether pre-procedural or technical modifications can mitigate complication rates. Thus, we sought to review the safety results at our institution where a uniformed pre-biopsy protocol has been in place for nearly two decades. METHODS: The records from 3,194 unique patients in the Portland Veterans Affairs Medical Center (VAMC) database who underwent transrectal ultrasound (TRUS) with initial prostate biopsy were reviewed. All patients had a normal urinalysis and no signs of prostatitis. All patients received a cleansing enema and antibiotic prophylaxis consistent with 2010 AUA guidelines, most commonly a one-day course of an oral flouroquinolone. All patients received a post-procedure telephone call within 2 weeks and any adverse effects were recorded. Rate of complications were assessed for the entire group and by study period (pre-2001 vs. 2001–2005 vs 2006–2010). RESULTS: Of all 3,194 patients who underwent the initial TRUS biopsy, complications occurred in 27 pts. (0.85%). These were classified as infectious in 18 pts (0.56%), clinically significant hematuria in 4 pts. (0.16%) and urinary retention in 5 pts. (0.13%). Hospital admission was required in 11 pts. (0.34%). There was a slight trend towards increased infectious complications in the two groups undergoing biopsy between 2001–2010 as compared to the pre-2001 group. CONCLUSIONS: Due to the emergence of antimicrobial-resistant organisms pre-procedure strategies that offset infectious complications are desperately needed. In our experience, strict adherence with a uniformed pre-procedure regimen resulted in a reduced rate of infections and hospitalizations as compared to historical controls. Based on these findings, the impact of ancillary measures prior to prostate biopsy procedures as a means of infection control is worthy of further study.