Objectives <p>Road traffic injuries (RTIs) constitute a serious challenge for human societies, imposing a substantial economic burden on countries and representing the leading cause of death among children and youth between the ages of 5 and 29. Estimates indicate that RTIs are on track to become the fifth leading cause of death globally by 2030. The aim of this study was to estimate the economic burden of RTIs in Bushehr Province and consequently in Iran in 2021–2022.</p> Methods <p>This is an incidence-based and cost-of-illness analysis study conducted from a societal perspective using recorded data on road traffic accidents during 2021–2022 years in the Hospital Information System (HIS) of hospitals affiliated to Bushehr University of Medical Sciences and also published information on RTIs by the Iran’s Statistical Centre. This study encompasses all individuals injured in road traffic accidents referred to the related hospitals. No sampling was employed in the investigation. The human capital approach was used to estimate the indirect costs and finally the bottom-up costing approach was used to calculate the total costs. Moreover, the uncertainty of the data was addressed by implementing a two-way sensitivity analysis.</p> Findings <p>The results demonstrated that in 2021 and 2022, the average annual cost of accidents per patient was 179,376.7 and 179,093.2 PPP$, respectively. Moreover, the largest proportion of costs was attributed to indirect expenses (95.7%), with lost income resulting from death accounting for the predominant share of indirect costs (equivalent to 75.3% of total indirect costs). The proportion of direct costs was found to be 4.3%, with the largest share of these costs attributable to salary expenditure, representing 34.3% of the overall direct costs. In addition, the economic burden of the disease in the country was estimated at 8,842,115,165 PPP $ over a two-year period. Given the sensitivity analysis, the economic burden of accidents in Bushehr province over a two-year period ranged from 132,184,254 to 1,003,055,017 PPP $, while the countrywide burden extended from 7,376,256,913 to 53,546,384,401 PPP $.</p> Conclusion <p>The findings revealed that RTIs impose a huge economic impact on households and society, with costs reaching 3.3% of GDP in Iran during the years 2021 and 2022, underscoring the necessity for policymakers to prioritize the reduction of this public health concern. Accordingly, establishing constructive inter-sectoral collaboration, Formulating and enforcing stricter driving laws, using the power of the media to educate the public and improving the safety of roads and vehicles is recommended.</p>