OBJECTIVES: The purpose of the review was to evaluate the efficacy and safety of escitalopram compared with sertraline and venlafaxine in treatment of major depressive disorder (MDD). METHODS: The analysis was performed in accordance with the rules of systematic review, based on Cochrane Collaboration guidelines and recommendations of Health Technology Assessment Agency in Poland (AOTM). RESULTS: In this report there were two subanalyses conducted, evaluating the efficacy and safety of escitalopram in comparison with sertraline and venlafaxine, both consisted of two multicenter, parallel-group, double-blinded, randomized clinical trials. In both comparisons efficacy was evaluated, based on the mean changes in MADRS, HAM-D, CGI-S, CES-D, HAM-A and CGI-I grading scales, as well as safety analysis was performed.Period of eight weeks treatment with escitalopram and sertraline as well as venlafaxine resulted in decrease in number of MDD symptoms and quality of life improvement. Over 50% decrease in number of major depression symptoms in MADRS and HAM-D grading scales compared to baseline indicates high clinical relevance of obtained results, even though statistical significance was not reached. Safety analysis showed similar safety profiles of all drugs taken into account. There were no statistical differences between populations in any of primary endpoints, except for withdrawals from the study due to adverse events in comparison of escitalopram vs venlafaxine favoring escitalopram. CONCLUSIONS: Escitalopram seems to be equally efficient and safe drug as sertraline and venlafaxine in treatment of patients with MDD. The clinical-effectiveness analysis ascertained equivalence of efficacy and similarity of safety profile of escitalopram in comparison with sertraline and venlafaxine in therapy of patients with MDD.