In May 2004 our institution encountered its first clinical isolate of linezolid-resistant, vancomycin-resistant Enterococcus faecium (LRVRE). Between October 2004 and July 2005, 40 patients from whom LRVRE organisms were recovered in clinical specimens were characterized. Epidemiologic investigation and pulsed-field gel electrophoresis patterns indicated a clonal outbreak related to nosocomial spread. Copyright © 2006, American Society for Microbiology. All Rights Reserved.