Background. Carbapenem-resistant Enterobacteriaceae (CRE) are rapidly emerging worldwide. Control group selection is critically important when analyzing predictors of antimicrobial resistance. Focusing on modifiable risk factors can optimize prevention and resource expenditures. To identify specific predictors of CRE, patients with CRE were compared with 3 control groups: (1) patients with extended-spectrum b-lactamase (ESBL)-producing Enterobacteriaceae, (2) patients with non-ESBL-containing Enterobacteriaceae, and (3) uninfected controls. Design. Matched multivariable analyses. Patients and setting. Patients possessing CRE that were isolated at Detroit Medical Center from September 1, 2008, to August 31, 2009. Methods. Patients were matched (1:1 ratio) to the 3 sets of controls. Matching parameters included (1) bacteria type, (2) hospital/ facility, (3) unit/clinic, (4) calendar year, and (5) time at risk (ie, from admission to culture). Matched multivariable analyses were conducted between uninfected controls and patients with CRE, ESBL, and non-ESBL Enterobacteriaceae. Models were also designed comparing patients with CRE to patients with ESBL, patients with non-ESBL Enterobacteriaceae, and all 3 non-CRE groups combined. results. Ninety-one unique patients with CRE were identified, and 6 matched models were constructed. Recent (less than 3 months) exposure to antibiotics was the only parameter that was consistently associated with CRE, regardless of the group to which CRE was compared, and was not independently associated with isolation of ESBL or non-ESBL Enterobacteriaceae. Conclusions. Exposure to antibiotics within 3 months was an independent predictor that characterized patients with CRE isolation. As a result, antimicrobial stewardship efforts need to become a major focus of preventive interventions. Regulatory focus regarding appropriate antimicrobial use might decrease the detrimental effects of antibiotic misuse and spread of CRE.