OBJECTIVES: The purpose was to conduct an economic analysis of escitalopram (generic drug) versus sertraline and venlafaxine as standard regimen in treatment of major depressive disorder (MDD) in Poland. METHODS: Due to lack of statistically significant differences in comparisons of escitalopram with sertraline and escitalopram with venlafaxine, economic profitability estimation was conducted as a cost-minimisation analysis (CMA). Decision model was created by using TreeAge® Pro. Data concerning efficacy and safety of compared therapies was based on the clinical-effectiveness analysis, which was conducted as systematic literature review. Total costs of analysed therapies were estimated from the perspective of both payers in Poland (National Health Fund and patient) and also from the social perspective. The time horizon of the analysis was 6 months. The costs were not discounted. The stability of results was checked in one-way and probabilistic sensitivity analyses. Additionally, optimistic and pessimistic scenarios were prepared. RESULTS: Based on the assumptions that clinical effects of compared treatment strategies are the same, the results of the cost-minimisation analysis are as following: treatment of one patient using escitalopram in the 6 month time horizon is 12.71 PLN more expensive then sertraline therapy and 135.95 PLN cheaper then therapy with venlafaxine. One-way sensitivity analysis conducted for comparison of escitalopram versus sertraline showed that results are sensitive on the prices of medicaments. The sensitivity analysis conducted for comparison of escitaloprom versus venlafaxine showed the stability of basic results. Therapy with escitalopram is cheaper than with venlafaxine for all parameters took into account in the sensitivity analysis. CONCLUSIONS: Escitalopram (generic drug) is costly comparable to sertraline and cheaper option of treatment in comparison with venlafaxine in the treatment of major depressive disorder in the 6 month time horizon.