Abstract: Background: Road Traffic Injuries (RTIs) as a result of road traffic crashes (RTCs) rank as the leading cause of death, disability and property loss worldwide, especially in low and middle-income countries. This study aims to analyze the costs of RTCs in Iran. Methods: A standard human capital approach was used to estimate the costs. Costs included medical, administrative and funeral costs, property damage, production lost and intangible costs. Data about the number of deaths and injuries resulting from RTIs between 20 March 2009 and 20 March 2010 was obtained from two national databases designed at the Center for Disaster Management and Medical Emergencies (CDMME) and the Legal Medicine Organization (LMO), respectively. The severity and medical costs of injuries were identified by reviewing 400 medical records that were selected randomly from patients who were admitted to two large trauma centers in Shariati and Sina hospitals in Tehran province. Moreover, information about production lost, property damage, rehabilitation cost, intangible costs and administration costs were collected by review of current evidence and consulting with expert opinion. Results: In total 806,922 RTIs and 22,974 deaths resulted from the RTCs in the study period. The total cost of RTCs was about 72,465 billion Rials (7.2 billion US Dollars), which amounts to 2.19% of Iran’s Gross Domestic Production (GDP). Direct costs were 3,516 billion Rials (around 48.6 % of the total costs), following by 24,785 billion Rials (around 34.2 % of the total costs) for production lost and 12,513 billion Rials (around 17.2 % of the total costs) for intangible costs. Conclusions: This study indicated that the burden of both RTCs and RTIs in Iran is substantial. Moreover, RTCs have significant economic consequences and are a large drain on healthcare resources.