OBJECTIVE: The EPHESUS study demonstrated that aldosterone blockade with eplerenone decreased mortality in patients with left ventricular systolic dysfunction (LVSD) and heart failure after acute myocardial infarction (AMI). The EPHESUS pharmacoeconomic analysis presented below was performed to evaluate the cost-effectiveness of eplerenone in the German setting. METHODS: A total of 6632 patients with LVSD and heart failure after AMI were randomized to eplerenone or placebo and followed for a mean of 16-months. The co-primary endpoints were all-cause death and the composite of cardiovascular death/cardiovascular hospitalization. The evaluation of resource use included hospitalizations, outpatient services, and medications. Survival beyond the trial period was estimated using data from the Framingham Heart Study, the Saskatchewan Health database, and the Worcester Heart Attack Registry. The incremental cost-effectiveness of eplerenone in cost per life-year and quality-adjusted life-year gained was estimated. RESULTS: The number of life-years gained with eplerenone was 0.1014 based on Framingham (95% CI: 0.0306-0.1740), 0.0636 with Saskatchewan (95% CI: 0.0229-0.1038) and 0.1337 (95% CI: 0.0438-0.2252) with Worcester survival estimates. Total costs were 961.2€ higher over the trial period in the eplerenone arm, due to drug cost. The incremental cost-effectiveness ratio was 9,173€ per life-year gained with Framingham (98.8% under 50,000€ per-life year gained), 14,627.8€ with Saskatchewan, and 6,955.6€ with Worcester survival estimates. CONCLUSION: Eplerenone is effective in reducing mortality and, in Germany, is also cost-effective in increasing years of life for patients with heart failure after AMI.