Background. This study aimed to identify risk factors associated with carbapenem-resistant Enterobacteriaceae (CRE) colonization among patients screened with rectal cultures upon admission to a hospital or long-term acute care (LTAC) center and to compare risk factors among patients who were screen positive for CRE at the time of hospital admission with those screen positive prior to LTAC admission. Methods. A retrospective nested matched case-control study was conducted from June 2009 to December 2011. Patients with recent LTAC exposure were screened for CRE carriage at the time of hospital admission, and patients admitted to a regional LTAC facility were screened prior to LTAC admission. Cases were patients with a positive CRE screening culture, and controls (matched in a 3: 1 ratio to cases) were patients with negative screening cultures. Results. Nine hundred five cultures were performed on 679 patients. Forty-eight (7.1%) cases were matched to 144 controls. One hundred fifty-eight patients were screened upon hospital admission and 521 prior to LTAC admission. Independent predictors for CRE colonization included Charlson's score greater than 3 (odds ratio [OR], 4.85 [95% confidence interval (CI), 1.64-14.41]), immunosuppression (OR, 3.92 [95% CI, 1.08-1.28]), presence of indwelling devices (OR, 5.21 [95% CI, 1.09-2.96]), and prior antimicrobial exposures (OR, 3.89 [95% CI, 0.71-21.47]). Risk factors among patients screened upon hospital admission were similar to the entire cohort. Among patients screened prior to LTAC admission, the characteristics of the CRE-colonized and noncolonized patients were similar. Conclusions. These results can be used to identify patients at increased risk for CRE colonization and to help target active surveillance programs in healthcare settings.