OBJECTIVE To evaluate the frequency and potential risk factors for infection-related complications after transrectal prostate biopsy and to propose adjustments in current antimicrobial prophylaxis recommendations. METHODS During 2008-2010, 107 patients underwent transrectal ultrasound-guided biopsies of the prostate at our institution. Charts were reviewed for infection-related complications within 30 days of the procedure. Potential risk factors were evaluated, including age, diabetes mellitus, chronic constipation/diverticular disease, prior use of quinolones, enema and prostatitis, on the pathology report. For patients with acute prostatitis, urine and blood samples were assessed for bacteriology and antibiotic susceptibility. RESULTS Of our 107 patients, acute prostatitis developed in 10 (9.3%). The most significant risk factor was prior use of a fluoroquinolone antimicrobial, with acute prostatitis developing in 7 (17.1%) of 41 patients who had used a fluoroquinolone compared with 3 (4.5%) of 66 patients who had not (P = .042). Patients who received an enema before the procedure were slightly less likely to develop prostatitis (P = .061). Of 8 positive specimens, the organisms isolated were Escherichia coli in 6, Klebsiella pneumoniae in 1, and Staphylococcus epidermidis in one. Isolated Gram-negative organisms were fluoroquinolone-resistant in 85.7% of samples. CONCLUSION Prior fluoroquinolone intake is a significant risk factor behind a rising incidence of acute prostatitis after transrectal prostate biopsy. Identified pathogens are mostly Gram-negative organisms with a high rate of fluoroquinolone resistance. Alternative prophylaxis regimens for the biopsy procedure should be considered in patients with recent quinolone intake. UROLOGY 78: 511-515, 2011. (C) 2011 Elsevier Inc.