Objective: To document the risk of the development of vancomycin-resistant bacteria in a population of seriously burned patients during a 10-year period of common vancomycin hydrochloride use. Design: Retrospective study. Setting: The US Army Institute of Surgical Research, Burn Center, Fort Sam Houston, Tex. Population and Methods: Microbiology, infection, and antibiotic use records collected during the hospitalization of 2266 consecutively admitted seriously burned patients were reviewed. Vancomycin was the primary therapeutic agent used for gram-positive infections and was also used as a perioperative prophylactic antibiotic during burn wound excision. This policy was established prior to this review because of a high incidence of methicillin-resistant Staphylococcus aureus colonization and an anecdotal association of increased beta-lactam resistance in endemic gramnegative pathogens associated with the use of penicillinase-resistant penicillins and cephalosporins. Main Outcome Measures: Isolation of vancomycin-resistant enterococci (VRE) or other gram-positive organisms resistant to vancomycin. Results: Examinations of 15 125 gram-positive isolates, including 957 enterococci, for in vitro sensitivity to vancomycin yielded 3 VRE isolates in 3 patients. Vancomycin was used prior to VRE isolation in one of these patients. Resistance was found in 3 other organisms (2 Corynebacterium species, 1 Lactobacillus species). Vancomycin was used prior to these isolations in 2 of 3 patients. None of the vancomycin-resistant organisms was associated with infection and all 6 patients survived. Vancomycin-resistant enterococci or other vancomycin-resistant gram-positive organisms were not found in 663 patients treated with vancomycin for documented gram-positive infections or in 1027 patients where perioperative vancomycin was used. Conclusion: Use of vancomycin as the primary therapeutic agent in seriously burned patients was not associated with increased risk of VRE isolation or VRE infection.