OBJECTIVES: The aim of this study is to estimate cost-effectiveness of lowering low-density lipoprotein cholesterol (LDL-C) with statin monotherapy in patients with elevated LDL-C with two or more cardiovascular risk factors or either coronary heart disease (CHD) in Spain. METHODS: A Markov model was developed to represent the transition of a cohort of patients with elevated LDL-C or with CHD at risk of a cardiovascular event (CVE) through four health states: patients with LDL-C, CVE, death by CVE and death by other causes. Probabilities of a CVE in females and males were determined, based on CHD risks estimated trough locally-adjusted Framingham risk equations using data from the DORICA and PRIMULA study. LDL-C lowering efficacy of statins, mortality, and health-state utilities were obtained from published scientific literature. Cardiovascular risk factors included were age, systolic blood pressure, diabetes, smoking and high-density lipoprotein cholesterol (HDL-C). Treatment and CVE direct medical costs were obtained from a medication database and DRGs for public hospitals in 2009 in Spain. Deterministic results were estimated and a probabilistic sensitivity analysis was conducted. Results were expressed as expected cost per quality adjusted life years (QALYs) gained. RESULTS: In deterministic analyses, expected costs per patient per year at age of 40 were higher for patients with 2 or more cardiovascular risk factors who were not treated than those who were treated (female: €41,300 vs. €40,106; male: €22,160 vs. €18,333). Effectiveness was higher for treated patients in both genders (female: 0.17 QALY; male: 0.37 QALY). Similar results were found for patients with CHD (female: €35,706 vs. €34,664, 0.10 QALY; male: €16,892 vs. €16,073, 0.12 QALY). CONCLUSIONS: From the perspective of the Spanish healthcare system, treatment with statin monotherapy is considered to be cost-effective versus no treatment in female and male patients with 2 or more risk factors or CHD.