BACKGROUND: Previous studies have suggested that living in a multi-generational household (a type of family structure prevalent in Japan) confers mixed health benefits and stresses, especially for women who report such living arrangements. OBJECTIVE: To examine, in a prospective cohort study, the impact of living arrangements on the incidence of coronary heart disease (CHD) and mortality as well as all-cause mortality in a large prospective cohort of the Japanese population. METHODS: The association between living arrangements and risk of CHD and mortality was examined prospectively within a cohort of 90 987 Japanese women and men aged 40-69 years, free of prior diagnosis of cancer and cardiovascular disease. A total of 671 cases of newly diagnosed CHD, 339 CHD deaths and 6255 all-cause deaths occurred between the baseline questionnaire (1990-4) and the end of follow-up in January 2004. RESULTS: After adjustment for potentially confounding variables, women living in multi-generational households (ie, with spouse-children-parents; or spouse-parents) had a two- to threefold higher risk of CHD than women living with spouses only. Women living with spouses and children also had a 2.1-fold higher risk of CHD incidence compared with married women living without children. CONCLUSIONS: Women in a multi-generational family had a higher risk of CHD, probably due to stress from multiple family roles.