Abstract: Objective To investigate the risk factors of carbapenem-resistant Enterobacteriaceae infection in intensive care unit (ICU). Methods From January 2016 to December 2017, 66 patients with Enterobacteriaceae infection resistance to carbapenem were selected as the main observation object (observation group), and carbapenem drug sensitivity in the same period of admission was selected as the main observation object (observation group). The demographic characteristics of 146 patients (control group) were collected. The basic clinical data, severity score, invasive operation and other general data were compared. The single factor difference between the two groups was determined by retrospective analysis, and multivariate Logistic regression analysis was used to identify the risk factors of carbapenem-resistant Enterobacteriaceae infection in intensive care unit (ICU). Results The incidence of carbapenem-resistant Enterobacteriaceae infection in intensive care unit was 31.13% (66/212). Among 66 strains of Enterobacteriaceae, 39 were Klebsiella pneumoniae (59.09%), 12 were Escherichia coli (18.18%), 11 were Enterobacter cloacae (16.67%), 4 were Enterobacter aerogenes (6.06%). There were significant differences in APACHE Ⅱ score, invasive operation and drug use before infection between patients with CRE infection and control group (P<0.05). The risk factors of APACHE Ⅱ score, operation, and endotracheal intubation were significantly different from those in control group (all P<0.05). Antibiotics were used before infection (OR>1; all P<0.05), and GCS score was the protective factor (OR<1; P<0.01). Conclusion The risk factors of Enterobacteriaceae infection in intensive care unit mainly included Apache Ⅱ score, operation, tracheal intubation and antibiotics before infection as protective factors, and Apache Ⅱ score was high. Severe coma patients undergoing surgery and endotracheal intubation should be given more attention and early screening if they have a history of antibiotic therapy.