We assessed the prevalence, risk factors, and clinical outcomes of patients co-colonized with vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA) upon admission to the medical and surgical intensive care units (ICUs) of a tertiary-care facility between January 1, 2002, and December 31, 2003. Co-colonization was defined as a VRE-positive perirectal surveillance culture with an MRSA-positive anterior nares surveillance culture collected concurrently. Among 2,440 patients, 65 (2.7%) were co-colonized. Independent risk factors included age (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.01-1.05), admission to the medical ICU (OR 4.38, 95% CI 2.46-7.81), male sex (OR 1.93, 95% CI 1.14-3.30), and receiving antimicrobial drugs on a previous admission within 1 year (OR 3.06, 95% CI 1.85-5.07). None of the co-colonized patients would have been identified with clinical cultures alone. We report a high prevalence of VRE/MRSA co-colonization upon admission to ICUs at a tertiary-care hospital.