Background: The National Cholesterol Education Program (NCEP) has designated high-density lipoprotein cholesterol (HDL-C) ≥60 mg/dL a 'negative' coronary heart disease (CHD) risk factor, but a substantial proportion of coronary events occur among women despite high HDL-C levels. Methods and Results: The objective of this study was to characterize postmenopausal women with prevalent CHD despite HDL-C ≥60 mg/dL and to identify factors that may attenuate the protective effect of high HDL-C. We analyzed baseline data from a randomized, double-blind study of estrogen/progestin replacement therapy in 2763 postmenopausal women <80 years old with CHD. Demographics, CHD risk factors, medications, anthropometrics, and lipid levels were compared among women with low, normal, and high HDL-C by NCEP criteria with and without stratification by use of lipid-lowering medications. Independent correlates of high HDL-C were determined by logistic regression analysis. HDL-C ≥60 mg/dL was present in 20% of participants. Women with high HDL-C were older, better educated, had fewer CHD risk factors, lower triglyceride levels and total cholesterol/HDL-C ratio, and were more likely to report past estrogen and current calcium antagonist, niacin, and statin use. β-Blocker, diuretic, and fibrate use was less common. Older age, alcohol consumption, niacin, and calcium antagonist use and prior estrogen use were independently associated with high HDL-C, whereas waist-to-hip ratio, smoking, triglyceride level, and β-blocker and fibrate use were inversely associated (all P < .05). Conclusions: High HDL-C, as defined by the NCEP, occurred in 20% of women with CHD in this cohort without a concomitantly higher prevalence of other CHD risk factors. Redefinition of 'high' HDL-C levels for women may be warranted.