OBJECTIVES: No studies to date have addressed the cost-effectiveness of lifelong dietary treatment when administered in “real world” community practice. This study examines whether a comprehensive intervention program to detect and treat, through dietary therapy, hypercholesterolemic patients is a cost-effective approach in the primary prevention of morbidity and mortality from coronary heart disease (CHD). METHODS: I developed a multidimensional model of CHD incidence using results from the Physician-Assisted Cholesterol Education Program (PACE), a prospective randomized trial in rural clinical practice, in combination with multivariate logistic risk functions from the Framingham Heart Study. The cost and health effects of this dietary intervention are projected over a lifetime for patients with known CHD risk factors. Results were also simulated for the pharmacologic treatment of lovastatin taken daily in addition to dietary intervention. Changes in life expectancy, quality-adjusted life expectancy, and incremental cost-effectiveness ratios ($/QALY), were the primary outcome measures of interest. RESULTS: PACE participants, on average, reduced their total serum cholesterol levels 1.3% (CI 0.43-2.14). Relative to no treatment, men on dietary treatment gained an estimated 4 to 26 days of quality-adjusted life expectancy at an estimated cost-effectiveness of $14,463 to $77,574 ($/QALY), depending on the age of treatment initiation. Women gained an estimated 3 to 19 days with cost-effectiveness ratios from $49,998 to $102,574 ($/QALY). Relative to dietary treatment alone, the cost-effectiveness of the combined diet-plus-lovastatin treatment ranged from $43,620 to $49,776 ($/QALY) in men, and from $52,996 to $74,718 ($/QALY) in women. CONCLUSIONS: Dietary intervention is a relatively cost-effective method of CHD prevention and should remain the preferred treatment option for younger men and women--especially for those initially at highest risk of CHD. Combined diet-plus-lovastatin therapy, however, is the optimal treatment choice for older individuals and for those who experience a reduced quality of life on stringent dietary regimes.