Objectives: Carbapenem-resistant Klebsiella pneumoniae (CRKP) has been increasingly reported all over the world. In this study, we aimed to investigate the risk factors for the acquisition of nosocomial CRKP infections. Methods: We conducted a case-control study with data collected from thirty-nine patients with nosocomially acquired CRKP infection between July 2006 and July 2008. Controls were selected at a ratio of 1:2 from patients with nosocomial carbapenem-susceptible Klebsiella pneumoniae (CSKP) infection and were matched with CRKP cases for site of infection and the date of hospital admission (+/- within 5 days). T test, chi-square test, and logistic regression were used for statistical analysis. Results: Bivariable analysis showed that the age of the patients (P = 0.038), days of hospital stay prior to isolation of Klebsiella pneumoniae (K. pneumoniae) (P = 0.043), altered consciousness (P = 0.007), intensive care unit (ICU) admission within two weeks (P = 0.003), tracheal intubation (P = 0.027), mechanical ventilation (P = 0.009), number of changes in antibiotics >= 4 (P = 0.001), exposure to carbapenems (P = 0.002), exposure to fourth-generation cephalosporins (P = 0.027), and exposure to piperacillin-tazobactams/cefoperazone-sulbactams (P = 0.043) and glycopeptides (P = 0.042) were related to CRKP infection. The multivariable analysis showed that ICU admission (within two weeks) [odds ratio (OR): 4.68, 95% confidence intervals (CI): 1.15-19.09, P = 0.031], exposure to carbapenems (OR: 12.69, 95% CI: 2.09 77.10, P = 0.006) and exposure to glycopeptides (OR: 3.57, 95% CI: 1.11-11.42, P = 0.032) were independent risk factors for nosocomial CRKP infections. Conclusion: Several factors are related to CRKP infections. ICU admission (within two weeks) or prior exposure to carbapenems or glycopeptides are independent risk factors for the acquisition of nosocomial CRKP infections.