The aim of this study was to assess infectious complications in transrectal ultrasound-guided prostate biopsy (TRUSPB), comparing two groups of patients: one group with antibiotic prophylaxis and the other without prophylaxis. A total of 1,018 TRUSPBs were performed from April 1996 to July 2003. No antibiotic prophylaxis was given in the first 614; the remaining 404 procedures were performed under antibiotic prophylaxis. Biopsy complications were assessed at outpatient urologist visits after the procedure in the 212 first biopsies and by telephone interview in the remaining 806. A total of 78 infectious complications were found. Major infectious complications (n=41) were septic shock (n=3), sepsis (n=3), Fournier gangrene (n=1), urinary tract infection (n=2), and fever requiring hospital admission (n=32). Minor infectious complications were fever that did not require admission (n=29), prostatitis (n=6), and epididymitis (n=2). Infectious complications occurred in 63 of 614 (10.3%) procedures without antibiotic prophylaxis and in 15 of 404 (3.7%) of those with antibiotic prophylaxis (P=0.0001). Of the 41 major infectious complications, 31 (75.6%) occurred in procedures without antibiotic prophylaxis (n=583) versus ten (24.4%) in those with prophylaxis (n=394) (P=0.0410). In conclusion, transrectal ultrasound-guided biopsy of the prostate has a statistically significant higher risk of infectious complications when performed without antibiotic prophylaxis.