A review of the cost-effectiveness literature indicated that the hydroxymethylglutaryl coenzyme A-reductase inhibitor fluvastatin is more cost-effective for achieving minor-to-moderate reductions in low-density lipoprotein cholesterol (LDL-C) levels than 3 other statins: lovastatin, pravastatin, and simvastatin. The main goal of this study was to verify the applicability of these conclusions to Spanish health care costs and patterns of resource consumption related to the treatment of hypercholesterolemia. A stochastic simulation model was used to predict both the costs and effects of treating high-risk hypercholesterolemic patients with fluvastatin, lovastatin, pravastatin, or simvastatin. Epidemiologic data were used to find a suitable theoretic probability distribution model for baseline LDL-C values in high-risk hypercholesterolemic patients. The model was then used to generate 10,000 random observations of baseline LDL-C values; the corresponding LDL-C values after a 2-year treatment period were predicted as a function of the baseline value and the percentage reduction expected with a particular statin and dose, according to the results obtained in 2 meta-analyses. The probability of treatment discontinuation was also taken into account using estimates obtained in usual practice. The effects of treatment were expressed as the rate of success in achieving the goal level of LDL-C, as defined in the current Spanish recommendations for the treatment of hypercholesterolemia. The average costs of treatment were computed from both the social and public-financing perspectives, including the cost of lipid-lowering drugs, physician visits, laboratory tests, and days off work, as appropriate. The occurrence of nonscheduled visits and workdays lost because of side effects were taken into account to compute indirect costs relevant to the social perspective. The potential costs of treating side effects were ignored. A cost-effectiveness analysis was performed to compare the cost-effectiveness ratios obtained with each of the 4 statins considered in this study. Model-based predictions of the effects, total costs, and cost-effectiveness ratios were made. Cost-effectiveness ratios were interpreted as the cost per patient meeting the goal of therapy, according to current Spanish recommendations. The data showed that fluvastatin had the lowest cost-effectiveness ratios when LDL-C levels required reduction to < or =25% of baseline levels. In this situation, fluvastatin was more cost-effective than lovastatin, pravastatin, or simvastatin from public-financing and social perspectives.