OBJECTIVE To compare treatment outcomes in patients with major depressive disorder treated with duloxetine, escitalopram, fluoxetine, paroxetine, or sertraline for up to 6 months. METHODS Data were taken from a 6-month prospective, observational study that included 1,549 major depressive disorder patients without sexual dysfunction in 12 countries. We report the overall results and those from Asian countries. Depression severity was measured using the Clinical Global Impression and the 16-item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16). Clinical and functional remissions were defined as having a QIDS-SR16 <6, and as having a rating of <3 on all three Sheehan Disability Scale items and no reduced productivity, respectively. Mixed effects modeling with repeated measures analysis and generalized estimating equation models were used. Propensity scores were included in the models. RESULTS The mixed effects modeling with repeated measures regression models showed that the Clinical Global Impression rating during follow-up was significantly lower in those patients treated with duloxetine compared with escitalopram (0.40, 95% CI 0.25 to 0.56); fluoxetine (0.22, 95% CI 0.05 to 0.38); paroxetine (0.38, 95% CI 0.23 to 0.54); and sertraline (0.32, 95% CI 0.16 to 0.49). The QIDS-SR16 of duloxetine-treated patients was significantly lower than those treated with escitalopram (1.58, 95% CI 1.03 to 2.12); fluoxetine (1.48, 95% CI 0.90 to 2.06); paroxetine (1.53, 95% CI 1.00 to 2.07); and sertraline (1.19, 95% CI 0.61 to 1.78). The probability of clinical remission of the patients treated with escitalopram, fluoxetine, paroxetine, and sertraline was lower than those treated with duloxetine (OR 0.46, 95% CI 0.33 to 0.64; OR 0.42, 95% CI 0.29 to 0.61; OR 0.40, 95% CI 0.29 to 0.56; OR 0.50, 95% CI 0.35 to 0.71; respectively). The regression analysis of functional remission also showed more favorable results for duloxetine, with OR ranging from 0.43, 95% CI 0.31 to 0.60 for paroxetine to 0.49, 95% CI 0.35 to 0.70 for sertraline. The results for the Asian countries were generally consistent. CONCLUSIONS Duloxetine-treated patients had better 6-month outcomes in terms of depression severity and clinical and functional remission, compared with selective serotonin reuptake inhibitor-treated patients.