OBJECTIVE: Among postmenopausal women, those with diabetes experience more cardiovascular diseases than those without diabetes. We examine the relationship of hormone replacement therapy (HRT) with indicators of lipid and glucose metabolism using a national sample of diabetic and nondiabetic postmenopausal women. RESEARCH DESIGN AND METHODS: We used data from the Third National Health and Nutrition Examination Survey, conducted from 1988 to 1994. A total of 2,786 postmenopausal women aged 40-74 years participated in an oral glucose tolerance test, had blood drawn for lipid assessment, and responded to HRT questions. RESULTS: Our results show that postmenopausal women with diabetes had increased dyslipidemia compared with nondiabetic women. Among diabetic women, current users of HRT had significant different lipid and glucose control levels than never users of HRT for the following variables: total cholesterol (225 vs. 241 mg/dl), non-HDL (169 vs. 188 mg/dl), apoA (171 vs. 147 mg/dl), fibrinogen (306 vs. 342 mg/dl), glucose (112 vs. 154 mg/dl), insulin (16.81 vs. 22.6 uU/ml), and GHb (6.03 vs. 7.13 mg/dl). CONCLUSIONS: Diabetic and nondiabetic postmenopausal women currently taking HRT had better lipoprotein profile than never or previous users of HRT. Diabetic women currently taking HRT had better glycemic control than never or previous users of HRT.