Background: Chronic heart failure (CHF) remains an important cause of morbidity and mortality worldwide. Currently, there are no cost-effectiveness studies of eplerenone use in patients with New York Heart Association (NYHA) class II CHF. Objective: We sought to evaluate the cost effectiveness of eplerenone compared with placebo in patients with chronic systolic heart failure and NYHA class II symptoms. Methods and results: A 10-year Markov model with yearly cycles was constructed to evaluate the cost effectiveness of eplerenone compared with placebo, based on data from the EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization And Survival Study in Heart Failure) study. The model classified subjects into two health states: Alive with CHF and Dead . Information about the cost of disease was derived from Australian Refined Diagnosis-Related Groups (AR-DRG) data. The cost of eplerenone was taken from the Australian Pharmaceutical Benefit Scheme. Utility data were derived from published sources, and a 5 annual discount rate was applied to future costs and benefits. Over 10 years, and compared with placebo, the model predicted that eplerenone would lead to a saving of 0.5 life-years (discounted) and 0.4 quality-adjusted life-years (QALYs) per person. The net cost was (in Australian dollars [ A]) A6,117 (discounted) per person. These equated to incremental cost-effectiveness ratios of A12,024 per life-year saved and A16,700 per QALY saved. Sensitivity analyses indicated that these results were robust. Conclusion: Eplerenone may represent a cost-effective strategy for preventing morbidity and mortality among patients with chronic systolic heart failure and NYHA class II symptoms.