Background: Although most observations in the Seven Countries Study suggest that cigarette smoking is harmful for health, universality of this conclusion remains controversial. Subjects and Methods: Cohort-specific and pooled smoking habits at baseline (1957-1964) in 12 763 men aged 40 through 59 years living in Europe, the United States, and Japan in relation to 25- year mortality follow-up. Pooled hazard ratios for smokers vs never smokers were calculated by the Cox proportional hazards model, adjusting for baseline country of residence, age, body mass index, serum cholesterol, systolic blood pressure, and clinical cardiovascular disease. Results: Adjusted hazard ratios for all-causes death in smokers compared with never smokers were 1.3 (95% confidence interval, 1.2-1.4) for smokers of less than 10 cigarettes per day and 1.8 (95% confidence interval, 1.7-1.9) for smokers of 10 cigarettes per day or more. Hazard ratios were elevated for death due to coronary heart disease, all stroke, other arterial disease, lung cancer, other cancer, chronic obstructive pulmonary disease, and other disease in smokers compared with never smokers. Within country, a few instances in which never smokers had a higher cause-specific death rate than smokers of 10 cigarettes per day or more were attributable to random variation associated with low prevalence of never smokers and multiple comparisons. Conclusions: These findings confirm the association of cigarette smoking with elevated risk of mortality from all causes, several cardiovascular diseases, cancer, and chronic obstructive pulmonary disease. Risk associated with cigarette smoking is independent of culture.