Background: A growing number of women provide care to disabled or ill relatives. Many studies have linked caregiving to psychiatric morbidity, lower perceived health status, elevated blood pressure, and poorer immune function. However, no studies have examined the association between caregiving and cardiovascular disease incidence. Methods: We conducted the study in 54,412 women from the Nurses' Health Study, a prospective cohort of female registered nurses residing in 11 U.S. states. These women were aged 46 to 71 years and did not have diagnosed coronary heart disease (CHD), stroke, or cancer at baseline (1992). We collected information on caregiving responsibilities in 1992 and coronary heart disease between baseline (June 1, 1992) and return of the 1996 questionnaire. Results: During 4 years of follow-up, we documented 321 incident cases of CHD (231 nonfatal cases of myocardial infarction and 90 CHD deaths). In multivariate analyses controlling for age, smoking, exercise, alcohol intake, body mass index, history of hypertension, diabetes mellitus, and other covariates, caregiving for disabled or ill spouse for ≥9 hours per week was associated with increased risk of CHD (RR, 1.82; 95% confidence interval, 1.08-3.05). However, caregiving for disabled or ill parents or disabled or ill others was not significantly associated with increased risks of CHD. Conclusion: These data indicate that high levels of caregiving burden for ill spouses may increase the risk of CHD among women.