Background and Objectives Non-interventional studies are a valuable source of evidence that is complementary to traditional randomised, blinded and controlled clinical trials, for evaluating antidepressants in a real-world setting. The aim of the present study was to document the use of agomelatine in current medical practice and evaluate its effectiveness and safety in outpatients prescribed agomelatine to treat their current depressive episode. Methods This 12-month observational French study included patients initiating agomelatine treatment. The intensity and severity of depression were assessed using the 17-item Hamilton Depression Rating Scale (HAM-D17) total score and the Clinical Global Impression-Severity of Illness (CGI-S) scale. Patients’ quality of life and functioning were measured using the Quality of Life in Depression Scale and the Sheehan Disability Scale, respectively. The safety measures included emergent adverse events and biological samplings, with a focus on liver acceptability. Results A total of 1484 patients (70% of women; 49.6 ± 15.4 years of age) were enrolled in the study. Most patients (62.3%) were treated with agomelatine for at least 6 months and 28.8% were treated for at least 1 year. Mean HAM-D17 total score and mean CGI-S scores decreased by 13.6 ± 8.1 and 2.1 ± 1.5 points, respectively, from baseline to last visit on agomelatine. Rates of responders (i.e. with a decrease in HAM-D17 total score by at least 50%) and remitters (HAM-D total score < 7) at the last visit were 90.7% and 56.0%, respectively. The mean HAM-D total score decreased after agomelatine withdrawal (− 4.1 ± 6.7) until the last visit. The quality of life and daily functioning of patients improved, while the numbers of days lost and underproductive days decreased over the follow-up period. Safety findings were in accordance with the known information regarding agomelatine. Conclusion In the current medical practice, this study confirms the effectiveness and good tolerability of agomelatine administered for a treatment period in agreement with guideline recommendations.< Réduire