A prospective cohort study with culture surveys and chart reviews was conducted to determine the prevalence of rectal colonization with vancomycin-resistant enterococci (VRE) and to identify risk factors for colonization among 100 residents of 20 different long-term care facilities (LTCFs) who were admitted to 2 medical wards of an academic acute care hospital. On admission to the hospital, 45 (45%) of these 100 patients were determined to be harboring VRE. Prior use of antibiotics and the presence of a decubitus ulcer were identified as risk factors. Fourteen other LTCF residents-33% of those at risk-acquired VRE in the hospital. Antecubital skin colonization with VRE was detected in 28% of patients. Hospital ward surveillance revealed a 60% mean point prevalence of VRE colonization among patients in LTCFs, compared with 21% for other patients (P<.001). Patients in LTCFs in urban referral hospitals are a major reservoir for VRE, which can be transmitted to other inpatients in the hospital, in the LTCF, and in smaller community hospitals.