BACKGROUND: A large number of depressed patients remained unremitting despite existing classes of antidepressants(SSRI,SNRI and NaSSa). Should Agomelatine, a new class of antidepressant reflect different clinical value in daily practice? OBJECTIVES: To evaluate clinical value and safety of Agomelatine on basis of daily practice in management of depressive disorders.  METHODS: Newly diagnosed depressed and unremitting depressed patients diagnosed by psychiatrists (per DSM-IV criteria) were prescribed Agomelatine 25 mg daily, followed-up at week 2, 6, 12 respectively. At follow-up, efficacy of Agomelatine were assessed with the 10-items standardized Thai version MÄDRS, Clinical Global Improvement score (both CGI-S, CGI-I) by psychiatrists. Acceptability and safety were assessed through direct patients’ interviews.  RESULTS: 133 depressed patients, mean duration of illness of 4.3 years, mean number of episodes of 2.4. Anxiety disorder and Insomnia were diagnosed in 12.8% and 8.3% of patients respectively. 63% and 37% of patients were treated with Agomelatine as monotherapy and combination with other psychotropic agents. The efficacy assessment as reflected by mean MÄDRS score reduction based on MÄDRS severity level. The mean(±SD) MÄDRS score for all patients (N=133), patients with MÄDRS < 20(N=67), MÄDRS between 20-24(N=32) and MÄDRS ≥ 25(N=34) at baseline of 21.40(5.25) ,16.91(1.75), 23.6(1.38) and 28.7(1.93) were significantly reduced with mean score reduction (95% CI)at p<0.001 by -10.2(9.3-11.1),- 6.3(5.8-6.8), - 11.2(10.0-12.5) and - 16.9(15.5-18.2) at the end of 12-weeks respectively. The clinical global improvement of depression after 12 week measured by mean (±SD) of CGI-S and CGI-I significantly improved for all patients at 1.65(±0.79) and 3.7(±1.02) respectively with therapeutic index of 2.52 (±1.11). The reported adverse effects were mild and transient, mainly dizziness and headache. No suspect case of abnormal liver enzyme was noted.  CONCLUSIONS: Agomelatine is a clinically effective, well-tolerated antidepressant in Thai depressed patients whatever the severity of depression. Agomelatine is endowed with moderate to high therapeutic value for management of depressive disorders in Thailand.