OBJECTIVE: To determine the epidemiology of colonization with vancomycin-resistant Enterococcus (VRE) among intensive care unit (ICU) patients. DESIGN: Ten-month prospective cohort study. SETTING: A 19-bed medical ICU of a 1,440-bed teaching hospital. METHODS: Patients admitted to the ICU had rectal swab cultures for VRE on admission and weekly thereafter. VRE-positive patients were cared for using contact precautions. Clinical data, including microbiology reports, were collected prospectively during the ICU stay. RESULTS: Of 519 patients who had admission stool cultures, 127 (25%) had cultures that were positive for VRE. Risk factors for VRE colonization identified by multiple logistic regression analysis were hospital stay greater than 3 days prior to ICU admission (adjusted odds ratio [AOR], 3.6; 95% confidence interval [CI95], 2.3 to 5.7), chronic dialysis (AOR, 2.4; CI95, 1.2 to 4.5), and having been admitted to the study hospital one to two times (AOR, 2.3; CI95, 1.4 to 3.8) or more than two times (AOR, 6.5; CI95, 3.7 to 11.6) within the past 12 months. Of the 352 VRE-negative patients who had one or more follow-up cultures, 74 (21%) became VRE positive during their ICU stay (27 cases per 1,000 patient-ICU days). CONCLUSION: The prevalence of VRE culture positivity on ICU admission was high and a sizable fraction of ICU patients became VRE positive during their ICU stay despite contact precautions for VRE-positive patients. This was likely due in large part to prior VRE exposures in the rest of the hospital where these control measures were not being used.