Objective To explore the epidemiological characteristics of ventilator-associated pneumonia (VAP) in adult intensive care units (ICUs) and the intervention effect of multimodal promotion strategies in the context of high prevalence of multidrug-resistant organism (MDRO). Methods The VAP surveillance data in the adult ICUs of a tertiary first-class hospital from January 2018 to December 2024 were selected, and the incidence, pathogens, and distribution of MDRO of VAP were analyzed. Changes in hand hygiene compliance rate, awareness rate, and implementation rate of prevention and control measures, as well as incidences of VAP before and after the implementation of multimodal promotion strategies were compared. Results From 2018 to 2024, a total of 115 525 days of invasive mechanical ventilation were surveilled, and 574 cases of VAP occurred, with a daily VAP incidence of 4.97‰. The pathogens were mainly Gram-negative bacteria (n=888, 81.69%), and the top three detected pathogens were Acinetobacter baumannii (n=279, 25.67%), Klebsiella pneumoniae (n=188, 17.29%), and Pseudomonas aeruginosa (n=185, 17.02%). The detection rates of carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Pseudomonas aeruginosa (CRPA), and methicillin-resistant Staphylococcus aureus (MRSA) in VAP patients in adult ICUs were all higher than the MDRO detection rates of corresponding bacteria in the whole hospital during the same period (all P<0.05). After implementing multimodal promotion strategies, healthcare workers’ compliance rate of hand hygiene, awareness rate of VAP prevention and control measures, and implementation rate of VAP prevention and control measures all improved significantly (all P<0.05); After implementing multimodal promotion strategies, the overall incidence of VAP of adult ICUs (3.56 ‰) decreased significantly compared with before implementation (6.54 ‰), difference was statistically significant (P<0.001). Conclusion Multimodal promotion strategies can effectively improve the compliance of VAP prevention and control measures and decrease the incidence of VAP in ICU patients, especially in departments with high prevalence of MDRO, provide basis for precise prevention and control.