OBJECTIVES Cardiovascular disease (CVD) is a leading cause of death in the US, but regular use of preventive low-dose aspirin has proven to be an effective way to prevent CV events. The purpose of this study was to explore the potential economic impact in the US if aspirin usage were to be increased in line with current clinical guidelines for primary and secondary prevention of CV events. METHODS The risk profile of the US population was modeled using NHANES data and the Framingham cardiovascular risk equations were applied to calculate risk for myocardial infarction, angina and stroke according to age and gender. Primary and secondary prevention patient populations were considered separately. Using publicly available unit costs, a budget impact model calculated the annual impact of increased preventive aspirin usage considering adverse events and diminishing aspirin adherence over a ten-year time horizon. RESULTS In a base population of 1,000,000 patients, implementation of current clinical guidelines would prevent an additional 1273 myocardial infarctions, 2184 angina episodes and 565 strokes in primary prevention patients and an additional 578 myocardial infarctions, and 607 strokes in secondary prevention patients. Angina reduction was not assessed in secondary prevention patients. This represents a total savings to the Managed Care Organization (MCO) of $84.9 million for primary prevention and $32.7 million for secondary prevention and additional out of pocket expense to patients of $32.1 million for primary prevention and $2.9 million for secondary prevention for the cost of aspirin. CONCLUSIONS This model suggests that there is a strong economic case, both for payers as well as for society, to encourage aspirin use for patients at appropriate risk and per clinical guidelines. It also provides an example of how minimizing costs does not necessarily have to imply rationing of care.