BACKGROUND It is well established that subjects participating in controlled clinical trials may not be representative of patients seen in actual practice. Given that efficacy and safety of sertraline have been investigated almost exclusively in controlled clinical trials, the aim of this study was to investigate efficacy, safety, and predictors of treatment response to sertraline in routine clinical practice. METHODS A total of 1878 depressed outpatients (69.5% female; mean age, 50.3 years) participated in this prospective, open-label, non-interventional, postmarketing surveillance study of sertraline. The primary study outcome was change in depression severity as assessed independently with the Patient Health Questionnaire (PHQ-9) depression scale and Clinical Global Impression (CGI) scales after 12 weeks of treatment. Stepwise logistic regression analyses were used to identify independent predictors of treatment response. RESULTS Using standard criteria to define clinical improvement, responder rates were 87.7% (PHQ-9) and 87.2% (CGI), respectively. Remission, i.e. a PHQ-9 score of 5 or below, occurred in 56.9% of patients. Independent baseline predictors of CGI treatment response were: non-chronic course of depression (OR=2.8, p < 0.001), non-psychiatric treatment setting (OR=2.5, p < 0.001), absence of comorbid physical disease (OR=1.9, p < 0.001), depression-related work disability (OR=1.9, p < 0.001), and no previous antidepressant medication (OR=1.5, p=0.03). Adverse events were reported by 4.8% of patients. LIMITATIONS Lack of a control group limits the conclusions that can be drawn from this study. CONCLUSIONS For treatment of depressive disorders in routine outpatient settings, sertraline is safe and efficacious. Patients without prior episodes of depression, without medical comorbidity, and those with higher levels of depression-related functional limitations are most likely to respond to sertraline treatment.