Postmenopausal hormone replacement therapy (HRT) is one of the most commonly prescribed drug regimens in the United States. This use largely reflects the significant number of postmenopausal women in the United States, many of whom are choosing to take HRT to treat symptoms of menopause. A recent survey showed that 40% to 55% of postmenopausal women have used hormone replacement therapy at some time in their lives, with higher rates of use in women who have undergone hysterectomy. Also contributing to the high prevalence of use has been significant publicity to physicians and women regarding HRT.s effect on bone density and its potential effect in decreasing cardiovascular disease (CVD) morbidity and mortality, as well as potentially reducing several other serious diseases, such as Alzheimer.s Disease and colon cancer. Finally, because estrogen replacement therapy has been shown to favorably alter lipids, estrogen use is recommended as part of the National Cholesterol Education Program Guidelines for managing cholesterol, and this too has contributed to its frequent use. Of all the potential benefits of HRT, the one with the greatest potential public health impact is its possible role in preventing CVD, the leading cause of death among women in the United States. CVD includes coronary artery disease (CAD) and stroke. Unfortunately, despite many observational studies of HRT and CVD, a valid answer to the question of whether HRT is protective against CVD has not yet been provided in the medical literature, due to limitations of observational studies. However, evidence from 3 randomized controlled trials has recently been published and aids in evaluating this relationship. This systematic evidence review will summarize all epidemiologic studies evaluating the role of HRT in the primary prevention of CVD. Two important recent studies of the secondary prevention of CAD in postmenopausal women will also be reviewed because they are the only published randomized controlled trials of HRT in CVD and may provide insight to the primary prevention discussion.