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We conducted this study to estimate the association and population attributable risk (PAR) of smoking with all-cause and cause-specific mortality based on a general prospective cohort study in Japan. A total of 8,129 subjects (3,996 males and 4,133 females) aged 40 or over were analyzed. The follow-up period was from 1986 to 2003. Smoking habit was classified into three categories of never smoker, former smoker, and current smoker. The Cox proportional hazard model was used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). We also estimated the PAR of smoking, and calculated the 95% CI of PAR based on the bootstrap procedure. A total of 112,151 person-years were counted for 8,129 subjects over an average of 13.7 years of follow-up. The results showed that smoking increased the risk of dying from all cancers, cardiovascular, and respiratory diseases in both sexes. For all causes of death, smokers had a HR of 1.30 (95% CI: 1.09, 1.54), PAR of 13.1% (95% CI: 7.6, 22.3) in males, and HR of 1.81 (95% CI: 1.43, 2.29), and PAR of 6.1% (95% CI: 3.1, 9.3) in females compared to never smokers. These results confirm an increased risk of mortality from all causes, as well as from all cancers, cardiovascular disease, and respiratory disease in relation to smoking habit. Smoking is responsible for a considerable proportion of deaths due to all causes as well as cause-specific deaths. Population-based antismoking programs should be implemented to reduce such avoidable deaths.