The isolation of carbapenem-resistant Klebsiella pneumoniae (CRKP) has been increasingly reported. However, no study analyzing potential risk factors for the acquisition of CRKP has been published as of now. We therefore performed a case-control study to determine the risk factors for the acquisition of CRKP. CRKP was nosocomially isolated from 30 patients between January 1997 and August 2003. Control patients were randomly selected at a ratio of 4:1 from the same medical or surgical services from which patients were receiving care when isolation of CRKP occurred. Risk factors for CRKP were previous use of carbapenem (adjusted odds ratio [AOR], 28.68; 95% confidence interval [CI], 9.08-90.55) and cephalosporin (AOR, 4.10; 95% CI, 1.35-12.43). In contrast, previous use of fluoroquinolone was negatively associated with isolation of CRKP (AOR, 0.26; 95% CI 0.07-0.97); however, the possibility of selection bias cannot be ruled out. Our results suggest that the nosocomial isolation of CRKP is strongly favored by the selection pressure of carbapenem.