OBJECTIVES: Major depressive disorder (MDD) is an important public health problem in South Korea, with a lifetime prevalence of 6.7%. Current antidepressants do not fully meet needs in depression, so additional options are required. We assessed the cost-utility of vortioxetine (a new antidepressant with multimodal activity) versusvenlafaxine XR in MDD patients in South Korea initiating these antidepressants or switching to them due to inadequate response to previous treatment. METHODS: A one-year cost-utility analysis from a societal perspective was performed using an initial decision-tree model, which included suicide risk, followed by a Markov model (2-month cycles) for subsequent treatments. Remission, relapse and recovery were the main health states. In first line, efficacy at two months was derived from the Asian SOLUTION study (vortioxetine vs. venlafaxine XR; NCT01571453) and for switching patients from REVIVE (vortioxetine vs. agomelatine; NCT01488071) and STAR*D (pragmatic trial of several antidepressants). STAR*D was the efficacy source for subsequent lines of treatment. Adverse event probabilities were included to consider the impact on quality of life and costs. Utilities were derived from REVIVE and adverse event disutilities from the literature. Resource use and productivity estimates were obtained from a survey of 28 Korean physicians. Korean 2013/2014 costs were applied. Deterministic and probabilistic sensitivity analyses were conducted.  RESULTS: Vortioxetine dominated venlafaxine XR, with QALY gains of 0.0155 and a cost difference of KRW 576,433 [US$532] (KRW 3,334 [US$3] when productivity not considered) over one year. The model showed a greater proportion of patients in recovery after initial treatment with vortioxetine (31.4%) compared with venlafaxine XR (23.4%). These results were confirmed to be robust through sensitivity analysis; vortioxetine remained dominant in 97% of probabilistic simulations.  CONCLUSIONS: Vortioxetine dominated venlafaxine XR in South Korea and therefore appears to be a relevant treatment option for MDD patients initiating or switching therapy.