Carbapenem resistance among Gram-negative bacilli has become an increasingly serious problem worldwide, and the emergence and spread of carbapenem-resistant Escherichia coli (CREC) is also becoming a serious problem. To date, however, risk factors for CREC acquisition have not been determined, so we decided to evaluate this in hospitalized patients through matched case-control study. Nosocomially acquired CREC was isolated from 46 patients between January 1997 and December 2007. For each patient, 3 matched-control subjects were selected. Previous use of carbapenem (adjusted odds ratio [AOR], 6.50) and metronidazole (AOR, 4.25), the presence of biliary drainage catheter (AOR, 4.59), and prior hospital stay (AOR 1.02) were found as independent risk factors for CREC. Our results suggest that the nosocomial acquisition of CREC may be favored by the selection pressure of carbapenems and metronidazole and also related to prior hospital stay and the presence of biliary drainage catheter.