OBJECTIVES: The objective of this study was to estimate the total direct cost for the management of heart failure (HF) in Greece. METHODS: This is a sub-analysis of the health economic data on 307 patients with HF followed by eight different secondary and tertiary hospitals across Greece as part of the ESC Heart Failure Pilot Survey. The economic evaluation was conducted from the social security system perspective with 2014 as the reference year. Parametric and non-parametric tests have been used in order to identify the factors which affect the cost of the disease. Only direct costs have been estimated including costs of hospitalisations, medications, other relevant cardiovascular interventions, clinical and laboratory follow-up, for up to one year after the index hospitalisation. Whenever data were missing and unavailable in the literature, an external expert panel was used. RESULTS: The mean annual economic burden of the social security system per HF patient was estimated at €4,411±4,764, which accounts for more than a 25% of the national gross domestic product per capita. Assuming a HF prevalence of 1.5 - 2%, it is estimated that the total annual direct economic burden of the social security system ranges between €730 and €973 millions. The cost for the patients enrolled during HF hospitalisation was almost double of the outpatients. The mean cost of the index hospitalisation was €2,292±3,092 for a 7-day median length of stay. About two thirds of this cost is due to in-patient care. Hospitalisation and total costs were significantly higher in male patients with kidney dysfunction, S3 gallop at presentation and higher NYHA classes (p<0.05). Primary aetiology of HF was not a significant predictor of increased cost. CONCLUSIONS: HF imposes a significant economic burden for the Greek social security system and national economy, mainly because of the frequent, long and costly hospitalisations.