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Objectives: The purpose of the study was to estimate relative risk and attributable risk of 35 tobacco-related diseases and to compute total medical expenses on smoking by providing a cohort study with 20 years follow-up period. Methods: Smoking-attributable medical costs were calculated by applying the percentages of population attributable risks (PARs) to the estimated medical costs by the tobacco related diseases in 2012. In this study, PARs were obtained by using relative risks from the Korean Cancer Prevention Study and the previous studies, and population smoking prevalence surveyed in 1990 conducted by Korean Institute of Tuberculosis. Results: As a result, the medical expenses from tobacco use were 1,846,562,350,000 won (about 3.86% of total medical expenses). The top 5 medical expenses on tobacco-related diseases were ischemic heart diseases, cerebrovascular diseases, lung cancer, diabetes, and chronic obstructive pulmonary disease, re- spectively. More than a half percent of total medical expenses (about one billion dollars) were spent from these five, tobacco-related diseases. Conclusions: While the harmful effect of smoking is expected to have a steady increase for a while, anti- smoking policy should be reinforced to reduce the risk of disease incidence, and the medical expenses for treating the tobacco-related diseases.