OBJECTIVES: Major Depressive Disorder (MDD) is an important and growing health problem in Turkey. Inclusion of a new drug in the positive list for its treatment requires the proof of cost effectiveness. The objective of this study was to assess the cost effectiveness of Agomelatine versus Venlafaxine and Duloxetine in treatment of MDD in Turkey. The study was undertaken from the payer perspective. METHODS: A discrete event model, already validated by European health authorities was used to compare Agomelatine with Venlafaxine and Duloxetine. An indirect comparison was made between Agomelatine and Duloxetine. In order to reflect the real clinical practice, the model defined 3-6 months of treatment, however the maintenance phase, defined as the recommended time to prevent eventual recurrences, was modeled longer (12 weeks and 24 weeks).The clinical outcome was measured as life years in remission. All direct costs for the year 2011 were taken into account.  Costs and benefits were discounted by 3% and robustness of the results were tested by Monte Carlo simulation. RESULTS: Incremental Cost Effectiveness Ratios(ICER) were calculated and results were displayed as cost per additional life year in remission. The ICER was calculated as  –18,799 TL/year in remission for Agomelatine versus Venlafaxine and – 27,453 TL/year in remission for Agomelatine versus Duloxetine.  CONCLUSIONS: Agomelatine dominated Venlafaxine and Duloxetine in treatment of MDD in Turkey. Sensitivity analyses revealed that the results were robust.