Objectives : The purpose of this study was to determine the population-attributable risk (PAR) and estimate the total medical expenditure of the Korean National Health Insurance (KNHI) due to smoking. Methods : We used data from the Korean Cancer Prevention Study of 1,178,138 Koreans aged 30 to 95. These data were available from 1992 to 2003 and covered a long-term follow-up period among the Korean population. Results : The total medical expenditure of KNHI related to smoking increased by 27% from $324.9 million in 1999 to $413.7 million in 2003. By specific diseases, smoking-attributable KNHI medical expenditure was the highest for lung cancer ($74.2 million), followed by stroke ($65.3 million), COPD ($50.1 million), CHO ($49 million) and stomach cancer ($30 million). A total of 1.3 million KNHI patients were suffering from smoking-related diseases in 2003. We predicted rises in total KNHI medical expenditure related to smoking to $675.1 million (63% increase compared with that of 2003) and in the total number of KNHI patients suffering from smoking-related diseases to about 2.6million (an approximate 100% increase compared with those in 2003) in 2015. Conclusions : We found a substantial economic burden related to the high smoking prevalence in South Korea.