Recent lipid therapy clinical trials confirm the treatment recommendations of the National Cholesterol Education Program (NCEP) and extend the proven benefits of primary and secondary prevention to women, elderly, and high risk patients with average cholesterol. OBJECTIVE: The purpose of this study were to estimate and compare the size of the primary and secondary prevention population if lipid treatment recommendations were based on (1) the NCEP treatment guidelines and the baseline characteristics of (2) the primary prevention population in the West of Scotland Coronary Prevention Study (WOSCOPS) and the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS) (3) the secondary prevention population in the Cholesterol and Recurrent Events (CARE) trial and the Scandinavian Simvastatin Survival study (4S). METHODS: Phase 1 data from the third National Health and Nutrition Examination Survey was used for analysis. RESULTS: Following the current NCEP recommendations, 18.6 and 5.8 million adults would be candidates for primary prevention and secondary prevention intervention respectively. If the treatment guidelines were based on the characteristics of the WOSCOPS or AFCAPS patients, the size of the primary prevention population would increase by 12.2 million to 30.8 million. Extending the recommendation based on the characteristics of the CARE or the 4S study patients would increase the secondary prevention population size by 2 million to 7.8 million. CONCLUSION: Recent clinical trials suggest that more than 15% of U.S. adults would benefit from lipid-lowering therapy for primary and secondary prevention of heart disease. Cost-effectiveness evaluation of lipid-lowering strategies should be used as a guide to treatment decisions.