While fibrates are clinically recommended for patients with low HDL cholesterol, the pharmacoeconomic literature on U.S. FDA-approved fibrates (gemfibrozil and fenofibrate) is limited. OBJECTIVES: To determine the cost-effectiveness of the fibrates in the primary prevention of CHD events in patients with low-levels of HDL (<35mg/dl) from the societal perspective. METHODS: An economic model was created utilizing a hypothetical cohort of United States males and females aged 45-79, with low levels of HDL, and no history of CHD. The source of data for predicted probabilities, the expected mortality rates, CHD event related treatment costs (in year 2000 dollars) is from the literature including the VA-HIT study; and the model utilized a discount rate of 3% and a lifetime time horizon. A sensitivity analysis was performed to determine the robustness of the model. RESULTS: In the base case scenario, males are more cost-effective than females for both gemfibrozil and fenofibrate. For males, as age increases the ratios of cost-effectiveness in terms of cost per life year gained decreases ($31,286-$4,930 for gemfibrozil; $43,750-$8,991 for fenofibrate). In terms of cost per QALY, the ratios of cost-effectiveness decreases with age in addition to a slight increase at age 75 ($8,119-$4,641 for gemfibrozil; $11,354-$8,464 for fenofibrate). For females, the cost per life year gained ratios decrease with age with a slight increase at age 70 ($43,750-$8,991 for gemfibrozil; $56,999-$30,789 for fenofibrate). In contrast, the cost per QALY ratios of cost-effectiveness increases with age with higher ratios at age 75 than at age 45 ($15,371-$20,489 for gemfibrozil; $21,619-$28,425 for fenofibrate). The results of the sensitivity analysis were consistent with the results of the base case scenario. CONCLUSION: This economic model demonstrates that treating men with fibrates are more cost-effective than treating women at any age, and all cost-effectiveness ratios are less than a $50,000 threshold, except for 45 year-old women treated with fenofibrate.