The effects of estrogen replacement therapy on prognosis in women with established coronary disease remain uncertain. The authors conducted a retrospective cohort study of 726 women (mean age, 66.2 years) who survived first myocardial infarction to hospital discharge from 1980 through 1991, while enrolled at Group Health Cooperative of Puget Sound in western Washington State. Estrogen replacement therapy after myocardial infarction (122 women) was ascertained from computerized pharmacy records. Reinfarctions (n = 135) and deaths (n = 183) through 1993 were identified, and relative risks were calculated. The relative risk for reinfarction associated with current estrogen replacement therapy after myocardial infarction, adjusting for age and time since infarction, was 0.64 (95% confidence interval (CI) 0.32-1.30), and that for past estrogen replacement therapy was 0.90 (95% CI 0.62-1.31). The relative risk for all-cause mortality associated with current estrogen replacement therapy was 0.50 (95% CI 0.25-1.00), and that for past estrogen replacement therapy was 0.79 (95% CI 0.56-1.09). While estrogen users were less likely than nonusers to have a history of diabetes or congestive heart failure, adjustment for these and additional prognostic factors altered risk estimates only slightly. Estrogen replacement therapy after first myocardial infarction was not associated with increased risk of reinfarction or mortality. This study provides reassurance regarding the safety of estrogen replacement therapy after myocardial infarction in women.