OBJECTIVES: In the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS), eplerenone decreased cardiovascular mortality and deaths from any cause by 15% (p=0.008) in patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure. An economic evaluation was performed to asses the cost-effectiveness of epleronone vs. placebo through patient lifetime in the Spanish setting. METHODS: The cost-effectiveness of eplerenone in cost per Life-Year (LYG) and Quality-Adjusted-Life-Years (QALY) gained compared to placebo was estimated. Efficacy data from EPHESUS study during the 16 month follow-up period were used. Survival data beyond trial period were estimated from the Framingham Heart Study Registry. The study was carried out from societal perspective; therefore, only direct medical costs where included. Drug acquisition costs were priced at AWP (average wholesale price), €2007. Costs were obtained from Spanish databases. Costs and effects were discounted 3% annually. Sensitivity analyses were carried out based on alternative life-years gained estimates from the Saskatchewan Health database and Worcester Heart Attack Registry Data, (0.0636 and 0.1337 respectively). RESULTS: The number of LYG with eplerenone was 0.1014 based on Framingham. Cost was €1016.90 higher over the trial period in the eplerenone arm because of drug cost (€1,164.07). The Framingham incremental cost-effectiveness ratio (ICER) of eplerenone compared to placebo was 10,030€ per LYG and 15,047€ per QALY gained. Sensitivity analyses showed eplerenone was efficient under alternative life expectancy estimates: €15,99€ per LYG with Saskatchewan and €7,60€ per LYG with Worcester. CONCLUSIONS: Selective aldosterone blockade with eplerenone is a cost-effective strategy in post-AMI patients with heart failure in Spain. In addition to standard therapy, eplerenone prevents events, saves hospitalization resources and improves survival among these patients.