Depression is common in heart failure and is associated with increased mortality. Yet, it is often underdiagnosed and inadequately treated. Lack of disease-specific and easy-to-administer screening tools is one of the reasons for underdiagnosis of depression in heart failure. We examined the effect of depression, as diagnosed by a single question about depression caused by heart failure symptoms and affecting quality of life, in a propensity score-matched cohort of heart failure patients. Of the 581 patients enrolled in the quality-of-life sub-study of the Digitalis Investigation Group trial, 298 (51%) reported that their heart failure prevented them from living as they wanted during the last month by making them feel depressed. Seventy patients (23%) who reported that they felt "much" or "very much" depressed were considered depressed for the purpose of this study. We matched 47 (67%) of these depressed patients with 47 patients from among the 283 patients without depression. Kaplan-Meier and matched Cox regression analyses were used to estimate associations of depression with mortality and hospitalizations during a median follow up of 33 months. Compared with 8 (17%) deaths in patients in the non-depressed group, 19 (40%) of those in the depressed group died from all causes [unadjusted hazard ratio (HR), 1.55; 95% confidence interval (CI), 1.004-2.39; p=0.048]. Adjustment for propensity scores (adjusted HR, 1.77; 95% CI, 1.04-3.00; p=0.034) or other covariates (adjusted HR, 1.85; 95% CI, 1.12-3.04; p=0.016) did not alter the association between depression and mortality. The association, however, became marginally significant in the matched cohort (HR, 2.50; 95% CI, 0.97-6.44; p=0.058). There was no significant association between depression and hospitalization. Baseline depression, identified by a single disease-specific question, was associated with increased mortality among ambulatory chronic heart failure patients. © The American Society of Contemporary Medicine and Surgery All rights of any nature whatsoever reserved.