Background and Objective: The Intensive Care Unit (ICU) provides specialized care for critically ill patients with compromised immunity, undergoing invasive treatments and frequently receiving broad-spectrum antibiotics, resulting in a high incidence of multidrug resistance. This study aimed to analyze the characteristics of nosocomial infections with multidrug-resistant bacteria in the ICU and to examine their drug resistance. Materials and Methods: A total of 968 patients treated in the ICU of Hospital of Chengdu University of Traditional Chinese Medicine from January, 2021 to December, 2023 were retrospectively selected as the study subjects. The distribution of pathogens in infected cases, changes in major pathogens in different years, antibiotic resistance of major pathogens and changes in drug resistance of  major  pathogens  were  analyzed  and  the  differences  in  drug  resistance  of  major  pathogens  in  different  years  were  compared. Results: Among 968 patients, 1244 bacterial strains were cultured. The detection rate of Klebsiella pneumoniae showed a decreasing trend over the years, while the detection rate of Enterococcus faecium exhibited an increasing trend (p<0.05). Escherichia coli  exhibited the highest resistance to cefazolin, Klebsiella pneumoniae  showed the highest resistance to ampicillin and Pseudomonas aeruginosa had the highest resistance to ceftazidime. Conclusion: The pathogens in the ICU are diverse, with Escherichia coli and Enterococcus faecium being the most prevalent. The antibiotic resistance of these pathogens is concerning and has shown an increasing trend annually. It is recommended to judiciously select antibiotics for treatment in clinical settings.