The aim of this study was to simultaneously examine a wide range of risk factors and clinical characteristics in their predictive value for the 1-year severity of depressive symptoms. Data from 789 participants in the Netherlands Study of Depression and Anxiety (NESDA), a large psychiatric cohort study, with a major depressive disorder (MDD) at baseline were used. Depression severity at 1-year follow-up was studied using linear and multinomial logistic regression models. Results of the analyses showed that high neuroticism, no partner and older age were found predictive of a poorer outcome independent of baseline clinical characteristics. Further, comorbid anxiety disorder, first episode, having a moderate subtype (vs. melancholic), and higher baseline depression severity predicted poorer outcome. To conclude, both risk factors and clinical characteristics independently predicted 1-year severity of depressive symptoms. The findings indicate that the prediction of prognosis and identification of persons at risk of a poor outcome should not only be based on clinical characteristics, but on risk factors as well.