BACKGROUND: Whether course trajectories of depressive and anxiety disorders are different, remains an important question for clinical practice and informs future psychiatric nosology. This longitudinal study compares depressive and anxiety disorders in terms of diagnostic and symptom course trajectories, and examines clinical prognostic factors. METHODS: Data are from 1209 depressive and/or anxiety patients residing in primary and specialized care settings, participating in the Netherlands Study of Depression and Anxiety. Diagnostic and Life Chart Interviews provided 2-year course information. RESULTS: Course was more favorable for pure depression (n=267, median episode duration = 6 months, 24.5% chronic) than for pure anxiety (n=487, median duration = 16 months, 41.9% chronic). Worst course was observed in the comorbid depression-anxiety group (n=455, median duration > 24 months, 56.8% chronic). Independent predictors of poor diagnostic and symptom trajectory outcomes were severity and duration of index episode, comorbid depression-anxiety, earlier onset age and older age. With only these factors a reasonable discriminative ability (C-statistic 0.72-0.77) was reached in predicting 2-year prognosis. LIMITATION: Depression and anxiety cases concern prevalent - not incident - cases. This, however, reflects the actual patient population in primary and specialized care settings. CONCLUSIONS: Their differential course trajectory justifies separate consideration of pure depression, pure anxiety and comorbid anxiety-depression in clinical practice and psychiatric nosology.