The evidence of the economic burden of road traffic injuries (RTIs) in Nepal is limited. The most recent study, conducted in 2008, is now considered outdated because there has been a rapid increase in vehicle numbers and extensive road building over the last decade. This study estimated the current economic costs of RTIs in Nepal, including the direct costs, productivity costs, and valuation of pain, grief, and suffering. An incidence-based cost-of-illness analysis was conducted from a societal perspective, employing a bottom-up approach using secondary data. All costs incurred by the patients, their family members, and costs to society were estimated, with sensitivity analyses to consider uncertainty around the data estimates available. Productivity loss was valued using the human capital approach. The total costs of RTIs in 2017 were estimated at USD 122.88 million. Of these, the costs of productivity loss were USD 91.57 million (74.52%) and the pain, grief, and suffering costs were USD 18.31 million (14.90%). The direct non-medical costs were USD 11.50 million (9.36%) whereas the direct medical costs were USD 1.50 million (1.22%). The economic costs of RTIs increased by threefold since 2007 and are equivalent to 1.52% of the gross national product, indicating the growing national financial burden associated with preventable RTIs.