OBJECTIVE- The effect of hormone replacement therapy on the risk of myocardial infarction in diabetic women has not been well studied. We conducted a case-control study of postmenopausal estrogen use and risk of incident myocardial infarction (MI) in pharmacologically treated diabetic women enrolled at Group Health Cooperative of Puget Sound, a large health maintenance organization in the state of Washington. RESEARCH DESIGN AND METHODS- Case subjects (n = 212) were all postmenopausal women with treated diabetes who sustained an incident fatal or nonfatal MI between July 1986 and December 1994. Control subjects (n = 122) were treated diabetic women drawn from a stratified random sample of postmenopausal women without prior MI. Computerized pharmacy data and medical records were used to measure use of estrogens. Cardiovascular risk factors recorded from medical records, computerized pharmacy and laboratory data, and telephone interviews were used as adjustment variables. RESULTS- In this study, 8.5% of case and 13.9% of control subjects were current users of estrogens. The relative risk (RR) of MI for current estrogen users was 0.51 (95% CI 0.22-1.15) relative to never users, adjusted for age, study year, weight, angina, and duration of treated diabetes. Among current estrogen users, risk of MI tended to decline with each additional year of estrogen use (adjusted RR = 0.78, 95% CI 0.56-1.08). Of those studied, 45.3% of case and 37.7% of control subjects were past users of estrogens (adjusted RR = 1.22, 95% CI 0.71-2.09). CONCLUSIONS- This study suggests that use of postmenopausal estrogens does not increase risk of M1 in diabetic women and that sustained use may be of benefit.