OBJECTIVE: The treatment of Major Depressive Disorder (MDD) represents a substantial financial burden to modern health care systems. The 12-month prevalence is estimated to be 12% in adult patients. Selective serotoninreuptake-inhibitors (SSRI) such as Escitalopram and Venlafaxin XR play an important role in treating that disorder in primary care. We demonstrate the cost-effectiveness of Escitalopram for Germany measured by successfully treated patients. METHODS: A markov-model over a horizon of 70 days with three markov-stages (remission, partial response, no response) was constructed. Due to the fact that the perspective of the physician was taken, only costs for medication have been considered. In order to include therapeutic decisions of physicians in a naturalistic matter, a survey of 190 GPs and 60 specialists has been conducted. RESULTS: Escitalopram has a 30% (GP: 113 vs. 144 €/successfully treated patient, specialist: 123 vs. 163 €/successfully treated patient) more favourable cost-effectiveness ratio compared with Venlafaxin XR. Depending on the setting (GP/ Specialist) the incremental cost-effectiveness ratio is considered to be 6800-7400€. The lower costs in the GPs model are due to referrals to specialists, since from the GPs perspective no further costs occur. CONCLUSIONS: Escitalopram is a cost-effective alternative to Venlafaxin XR for the treatment of MDD in the German setting.