Late Dr Takeshi Hirayama and his colleagues conducted a mortality follow-up of a large-scale cohort in six prefectures in Japan. This study is called the six-prefecture cohort study or Hirayama Cohort Study. The study subjects were residents aged 40 years or older at the baseline survey in 1965, which covered 94.8% of residents identified in the study area by the National Census conducted on October 1, 1965. The mortality of 264,118 cohort members was followed until the end of 1982. One of the most important findings made by this study was an association between second-hand smoke exposure and lung cancer. This finding is the origin of the worldwide spread of smoking ban in indoor public venues and workplaces. Other major findings obtained from the study are also briefly described in this article.