Cardiovascular disease (CVD) accounts for 34% of overall mortality in the United States or an average of 1 death every 38 seconds. While the majority of these events are related to coronary heart disease (CHD), stroke accounts for a sizeable burden of CVD among postmenopausal women. Before 75 years of age, a higher proportion of CVD events due to CHD occur in men than in women, as opposed to a higher proportion of events due to stroke occurring in women. Sex-based disparities in medical care are well documented, and under-treatment of women with aspirin for secondary prevention of CVD is a blatant example of the quality chasm described in the Institute of Medicine report "between the care we have and the care we could have". However, while aspirin appears to be of substantial net benefit in secondary prevention, the balance of its beneficial effects and bleeding hazards in primary prevention remains less certain, especially in women. The current review examines the evidence and provides recommendations for the use of aspirin for primary prevention of CVD in women.