Background: To estimate the economic loss due to road traffic injuries (RTIs) of the World Health Organization (WHO) member countries and to explore the relationship between the economic loss and relevant health system factors. Methods: Data from the World Bank and the WHO were applied to set up the databases. Disability-adjusted life year (DALY) and gross domestic product per capita were used to estimate the economic loss relating to RTIs. Regression analysis was used. Data were analyzed by IBM SPSS Statistics, Versions 20.0. Results: In 2005, the total economic loss of RTIs was estimated to be 167,752.4 million United States Dollars. High income countries (HIC) showed the greatest economic losses. The majority (96%) of the top 25 countries with the greatest DALY losses are low and middle income countries while 48% of the top 25 countries with the highest economic losses are HIC. The linear regression model indicates an inverse relationship between nurse density in the health system and economic loss due to RTI. Conclusions: RTIs cause enormous death and DALYs loss in low-middle income countries and enormous economic loss in HIC. More road traffic prevention programs should be promoted in these areas to reduce both incidence and economic burden of RTIs.