Introduction: Meta-analyses are useful to increase knowledge and strengthen evidence about antidepressant treatment supplementary to individual studies. Methods: A pooled analysis of four multicenter, open-label, prospective, non-interventional studies (2009-2013) was performed to provide further evidence about the antidepressant effectiveness and tolerability of agomelatine (25-50 mg/day) in a large number of non-selected German outpatients with major depressive disorder. The main analysis was performed after 12 weeks (n = 9601) and in subpopulations after 24 and 52 weeks by descriptive statistical methods. Results: Overall, 60.1% of patients were pre-treated with antidepressants. Concomitant psychiatric diseases (71.9%), co-medication with antidepressants (18.9%) and/or psychotropic medication (31.9%) were observed. Depressive symptoms improved according to the Clinical Global Impression (CGI) in 81% after 12 weeks, a response was observed in 78.7% (CGI-I3 times upper normal value), with 19 patients (0.2%) showing preexisting elevations at the study start. One patient (0.03%) developed hepatitis with reversible symptoms after treatment discontinuation. ADR predominantly occurred within the first weeks of treatment. Mean weight and body mass index (BMI) remained unchanged over 24 weeks. Conclusion: In this pooled data analysis, 9601 depressed patients of clinical practice were evaluated over 12 weeks and subpopulations were also analyzed over 24 and 52 weeks. Agomelatine effectively reduced depressive symptoms (CGI-response and remission) with good general tolerability.