In a prospective clinical trial involving 482 acutely hospitalized patients, the overall incidence of catheter-associated urinary tract infection (UTI; 10%) was similar in recipients of a silver oxide-coated urinary catheter (silver catheter) or a control silicone catheter. However, female sex and absence of antimicrobial use were independently associated with an increased risk of UTI. After stratification for these variables, the silver catheter reduced the incidence of UTI among women not receiving antimicrobial agents (19% for control catheter vs. 0 for silver catheter, P = .04; confidence interval for the difference in incidence, 0.4%-38%) but not in the other subgroups. Gram-positive UTI was associated with absence of antimicrobial use, the control catheter, and catheter care violations. Gram-negative and candidal UTIs were more common after 7 days of catheterization, and candidal UTI was associated with being female and antimicrobial use. These findings demonstrate that several clinical variables influenced the incidence and microbiology of catheter-associated UTI and that the silver catheter appeared to prevent UTI among women not receiving antimicrobials.