OBJECTIVES:  A cost-utility analysis of agomelatine, a  treatment of major depressive disorders in adults, was performed from the Polish public payer's perspective (the National Health Fund). Agomalatine was compared with the most commonly used antidepressants in Poland, i.e. generic sertraline and generic venlafaxine. METHODS: The analysis with a time horizon of 2 years is based on a Markov model. The one-month cycle model included the following health states: depression episode, remission, well and death. It also incorporated sleep disorders, discontinuation rates, discontinuation symptoms and adverse drug reactions. The clinical parameters for compared drugs were extracted from head-to-head clinical trials. Utility and disutility estimates were derived from a systematic literature review. Only direct costs have been considered in order to be consistent with Polish pharmacoeconomic guidelines. Costs and effects were discounted at 5% and 3.5% per annum at year 1 respectively. RESULTS: The benefit of agomelatine over sertraline or venlafaxine was estimated at 0.005 QALY. This effectiveness was associated with the additional costs of 491 PLN and 149 PLN for agomelatine compared to sertraline and venlafaxine, respectively. The corresponding  agomelatine incremental cost-utility ratios (ICURs) were therefore 92,000 PLN/QALY and 28,000 PLN/QALY. Sensitivity analysis demonstrated that agomelatine ICUR remained below the three times GDP per capita threshold (33,347 PLN for 2008) in 79.7% and 88.4% of the cases compared with sertraline and venlafaxine, respectively. CONCLUSIONS: From the Polish public payer 's perspective, agomelatine is a cost-effective treatment of major depressive disorders compared to generics of sertraline and venlafaxine.