Infection control practices are not uniformly successful in limiting outbreaks of vancomycin-resistant enterococci (VRE). Despite the implementation of barrier precautions for VRE-infected patients, nearly one-half of the inpatients at our center were found to have gastrointestinal colonization by VRE. In an attempt to control the outbreak, we altered the antibiotic formulary by restricting the use of cefotaxime and vancomycin and adding beta-lactamase inhibitors to replace third-generation cephalosporins. The use of clindamycin was also restricted because of a concomitant outbreak of Clostridium difficile colitis. After 6 months, the average monthly use of cefotaxime, ceftazidime, vancomycin, and clindamycin had decreased by 84%, 55%, 34%, and 80%, respectively (P < .02). The point prevalence of fecal colonization with VRE decreased from 47% to 15% (P < .001), and the number of patients whose clinical specimens were culture positive also gradually decreased. A change in antibiotic use appears to have significantly affected our VRE outbreak when previous measures failed.