Objective: Hospitalization for worsening heart failure (HF) is common and associated with high mortality. However, the effect of incident HF hospitalization (compared with no HF hospitalization) on subsequent mortality has not been studied in a propensity-matched population of chronic HF patients. Methods: In the Digitalis Investigation Group trial, 5501 patients had no HF hospitalizations (4512 alive at 2 years after randomization) and 1732 patients had HF hospitalizations during the first 2 years (1091 alive at 2 years). Propensity scores for incident HF hospitalization during the first 2 years after randomization were calculated for each patient and used to match 1057 patients (97%) who had 2-year HF hospitalization with 1057 patients who had no HF hospitalization. We used matched Cox regression analysis to estimate the effect of incident HF hospitalization during the first 2 years after randomization on post-2-year mortality. Results: Compared with 153 deaths (rate, 420/10,000 person-years) in the no HF hospitalization group, 334 deaths (rate, 964/10,000 person-years) occurred in the HF hospitalization group (hazard ratio 2.49; 95% confidence interval 1.97-3.13; P < .0001). The hazard ratios (95% confidence intervals) for cardiovascular and HF mortality were 2.88 (2.23-3.74; P < .0001) and 5.22 (3.34-8.15; P < .0001), respectively. Conclusions: Hospitalization for worsening HF was associated with increased risk of subsequent mortality in ambulatory patients with chronic HF. These results highlight the importance of HF hospitalization as a marker of disease progression and poor outcomes in chronic HF, reinforcing the need for prevention of HF hospitalizations and strategies to improve postdischarge outcomes. © 2008 Elsevier Inc. All rights reserved.