Objective To explore the temporal characteristics and independent risk factors of secondary infection after carbapenem-resistant Enterobacterales (CRE) intestinal colonization in patients in the intensive care unit (ICU), and provide basis for clinical prevention and control. Methods Patients who admitted to the respiratory/surgical ICU of a tertiary first-class hospital from January 2023 to June 2025 were analyzed retrospectively. Colonization was determined through active rectal swab/fecal screening, infection was diagnosed according to the "Diagnostic criteria for healthcare-associated infection". Patients were divided into infection group and colonization group based on secondary infection after CRE intestinal colonization. Clinical data of two groups of patients were collected for group comparison, risk factors for secondary infection after CRE intestinal colonization in ICU patients were analyzed by univariate and multivariate logistic regression. Results A total of 1 288 patients were included in analysis, out of which 132 had CRE intestinal colonization, with a colonization rate of 10.25%. Among patients with colonization, 43.94% (n=58) had secondary infection, with respiratory tract being the main infection site (64.62%), followed by blood (24.62%). The duration for secondary infection in patients with hospital-acquired colonization was 5 (2,7) days, which was shorter than that of patients with colonization at admission (12 [4,14] days; Z=-2.97, P=0.003). Univariate and multivariate logistic analysis showed that mechanical ventilation (OR=3.94, 95%CI: 1.60-9.66) and use of carbapenems (OR=7.93, 95%CI: 2.63-20.27) were independent risk factors for secondary infection after CRE intestinal colonization in ICU patients. Conclusion ICU patients have a higher risk of secondary infection after CRE colonization, and those with hospital-acquired colonization have faster progression of infection. Attention should be paid to patients with mechanical ventilation and those exposed to carbapenems, active screening and intervention should be strengthened to effectively control the occurrence of infection.