In May 2000, the first outbreak of vancomycin-resistant Enterococcus faecium (VREF) was detected in the University Medical Center Utrecht in the nephrology ward. The question arose why some VREF strains spread among hospitalized patients, whereas other strains do not. Thirty patients who were found to be colonized with VREF between May and November 2000 were included in the study. Molecular typing confirmed that 19 of them carried an identical epidemic strain which harbored the esp gene while 11 were colonized by nonepidemic strains that were all esp negative. Acquisition of the outbreak strain was significantly associated with diabetes mellitus, renal transplantation, and extensive use of antibiotics, especially cephalosporins, in the 2-month period before the first isolation of VREF. To establish the duration of colonization, prospective surveillance of VREF carriage for a 6-month period starting from the first isolation of VREF was realized for 20 patients. After 6 months, VREF was still recovered from 60% of carriers of the outbreak strain versus 20% of carriers of nonepidemic strains (P < 0.01). However, antibiotic use during the follow-up period was significantly higher by carriers of the outbreak strain than by carriers of nonepidemic strains. The fact that the outbreak strain was recovered for a longer period of time than nonepidemic strains may facilitate dissemination of the strain. The results support a careful restrictive antibiotic policy for wards at risk for spread of VREF and implementation of isolation precautions for patients who are colonized with esp-positive outbreak strains.