BackgroundHealthcare expenditure of road traffic injuries in China has not been adequately investigated so far. We aim to provide comprehensive information about the hospitalization costs of inpatients who suffered road traffic injuries, and explore the components and influencing factors of costs. MethodsWe extracted the data of all inpatients (n = 60535) with road traffic injuries during the year 2019 from Chinese National Health Statistics Network Reporting System database in Hunan, China. We calculated the components of hospitalization costs and analyzed the association between hospitalization costs and patient characteristics using quantile regression models. ResultsThe median hospitalization cost was $853.48, and the median length of hospital stay was 9 days. Vulnerable road users accounted for 84.9 % of all cases. Medicine cost is the first driver of hospitalization cost, accounting for 25.94 %. In the low- and medium-cost groups, hospitalization costs were highly concentrated on diagnosis, medicine, and medical services, while in the high-cost groups, consumable cost constituted the highest percentage. Male, a longer length of stay, more severe injuries, two or more comorbidities, surgical treatment, and admission to tertiary hospitals were significantly associated with higher hospitalization costs, and the regression coefficients increased with increasing of quartile points. Costs were lower in the 0–14 years group than in the other groups across all quartiles. At the median, occupants of heavy transport vehicle incurred the highest costs, $44.18 higher than pedestrians; injuries at lower extremities generated higher costs than those at any other site; and vascular injuries caused the greatest costs, $786.24 higher than superficial injuries. ConclusionsRoad traffic injuries cause huge healthcare costs for victims, most of whom are vulnerable road users. The total cost of hospitalization is incurred mainly for medicine, consumables, diagnosis, medical services, and treatment. Patients’ demographic factors (gender and age), clinical factors (injury severity, location, nature, and number of comorbidities), treatment factors (surgery, length of stay, and hospital level), and road user type are all significantly associated with hospitalization costs.