Objective To investigate the risk factors of multidrug-resistant organism (MDRO) infection in patients with car accident injuries in intensive care unit (ICU), providing clinical guidance for reducing MDRO infection in car accident patients. Methods The clinical data of patients with car accident injuries in Sichuan Provincial People’s Hospital between January 1st 2019 and February 28th 2023 were collected, and the relevant data were analyzed retrospectively to explore the risk factors of MDRO infection. Results A total of 141 patients with car accident injuries were collected, of whom 30 had MDRO infection. The proportions of males (P=0.012), indwelling catheters (P=0.005), mechanical ventilation (P=0.001), length of hospital stay (P<0.001), and total treatment costs (P<0.001) in the infection group were higher than those in the non-infection group. Multiple logistic regression analysis showed that male [odds ratio (OR)=3.797, 95% confidence interval (CI) (1.174, 12.275), P=0.026], mechanical ventilation [OR=4.596, 95%CI (1.538, 13.734), P=0.006], and length of hospital stay≥20 d [OR=1.014, 95%CI (1.001, 1.028), P=0.037] were independent risk factors for MDRO infection in car accident patients. Conclusions Male, mechanical ventilation, and increased length of hospital stay are independent risk factors for MDRO infection in car accident patients. For such patients, the prevention and control measures of hospital infection should be strictly implemented to reduce the risk of infection.