Background-Although studies have shown that depression is associated with worse outcomes in patients with heart failure, most studies have been in white patients. The impact of depression on outcomes in blacks with heart failure has not been studied. Methods and Results-We analyzed 747 blacks and 1420 whites enrolled in Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training, which randomized 2331 patients with ejection fraction ≤35% to usual care with or without exercise training. We examined the association between depressive symptoms assessed by the Beck Depression Inventory-II (BDI-II) at baseline and after 3 months with all-cause mortality/hospitalization. A race by baseline BDI-II interaction was observed (P=0.003) in which elevated baseline scores were associated with worse outcomes in blacks versus whites. In blacks, the association was nonlinear with a hazard ratio of 1.44 (95% confidence interval, 1.24-1.68) when comparing the 75th and 25th percentile of BDI-II (score of 15 and 5, respectively). No race interaction was observed for mortality (P=0.34). There was no differential association between BDI-II change and outcomes in blacks versus whites. In blacks, an increase in BDI-II score from baseline to 3 months was associated with increased mortality/hospitalization (hazard ratio, 1.33; 95% confidence interval, 1.12-1.57 per 10 point increase), whereas a decrease was not related to outcomes. Conclusions-In blacks with heart failure, baseline symptoms of depression and worsening of symptoms over time are associated with increased all-cause mortality/hospitalization. Routine assessment of depressive symptoms in blacks with heart failure may help guide management. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00047437.