Objective: Road Traffic Injuries (RTIs) are one of the most crucial and challenging public health problems in low and middle income countries. Despite continuous efforts to estimate both personal and societal costs of RTIs however, their long-term effects have remained marginal. The current study aimed to explore the economic burden of RTIs until one year after the victim's hospitalization. Methods: The study included a total of 1150 RTI victims, who were admitted to two trauma-referral hospitals during 2016. Data on direct medical costs, direct non-medical costs and indirect costs were gathered for each study sample via hospital records and phone surveys. Direct and indirect costs from a social perspective were estimated based on Micro Costing Approach followed by the Human Capital Approach. Also, the explanatory variables affecting the costs of RTIs were identified using the liner regression model. Results: The average amounts of direct (medical, non-medical), indirect, and total costs of RTI were estimated as 2,908 US$ (1,591 US$, 1,316 US$), 5,790 US$, and 8,701 US$ respectively. Also, several variables were significantly affecting the costs of RTIs including age, marital status, employment status, severity of injury, receiving physiotherapy care, victim's vehicle type in crash, crash time and location. Conclusions: Findings suggest that RTIs are considered as an enormous burden on Iranian GDP per capita and health expenditure per capita occupying 167% and 347% respectively. This enormous economic burden caused by RTIs requires more policy regulations and prevention programs to decrease RTIs.