Congestive heart failure (CHF) is frequently associated with depression. However, the impact of depression on prognosis has not yet been sufficiently established. To prospectively investigate the influence of depression on mortality in patients with CHF. In 209 CHF patients depression was assessed by the Hospital Anxiety and Depression Scale (HADS-D). Compared to survivors (n=164), non-survivors (n=45) were characterized by a higher New York Heart Association (NYHA) functional class (2.8+/-0.7 vs. 2.5+/-0.6), and a lower left ventricular ejection fraction (LVEF) (18+/-8 vs. 23+/-10%) and peakVO(2) (13.1+/-4.5 vs. 15.4+/-5.2 ml/kg/min) at baseline. Furthermore, non-survivors had a higher depression score (7.5+/-4.0 vs. 6.1+/-4.3) (all P<0.05). After a mean follow-up of 24.8 months the depression score was identified as a significant indicator of mortality (P<0.01). In multivariate analysis the depression score predicted mortality independent from NYHA functional class, LVEF and peakVO(2). Combination of depression score, LVEF and peakVO(2) allowed for a better risk stratification than combination of LVEF and peakVO(2) alone. The risk ratio for mortality in patients with an elevated depression score (i.e. above the median) rose over time to 8.2 after 30 months (CI 2.62-25.84). The depression score predicts mortality independent of somatic parameters in CHF patients not treated for depression. Its prognostic power increases over time and should, thus, be accounted for in risk stratification and therapy.