After noting a rise in vancomycin-resistant enterococci (VRE) infections, we initiated a program to decrease inappropriate vancomycin use that focused on improvement of house staff prescribing practices. The initial intervention in June, 1995, encouraging house staff to follow hospital guidelines for vancomycin use and eliciting support from service chiefs in this effort, had little impact. A more intensive educational intervention, beginning in January, 1996, involved concurrent review of all vancomycin orders and one-on-one discussion with the house staff regarding the rationale for the order by an infectious diseases clinical pharmacist. When usage was deemed inappropriate, the pharmacist asked that vancomycin be discontinued, but no automatic stop orders were issued. During the next two and one-half years, this second intervention proved effective at decreasing inappropriate use from 39% to 16.8% +/- 2.4% (p = 0.005). This change was primarily due to a decrease in appropriate vancomycin prophylaxis by cardiothoracic surgery. VRE infections decreased from 0.29/100 patients discharged prior to initiating the program to 0.13/100 patients discharged after the second intervention (p = 0.01). This educational program, although labor-intensive, preserved house staff decision-making skills related to antibiotic prescribing at the same time that it decreased inappropriate vancomycin use.