A high cardiothoracic ratio (CTR) is a marker of an enlarged heart and is associated with poor outcomes in patients with heart failure (HF). To what extent this association is independent of other confounders is not well known. However, to study this, propensity score matching was used to design a study in which HF patients with normal (≤0.50) and high (>0.50) CTRs were well balanced on all measured baseline covariates. In the Digitalis Investigation Group trial (n = 7,788), 4,690 patients had high (>0.50) CTRs. Propensity scores for high CTR were calculated for each patient and were then used to match 2,586 pairs of patients with normal and high CTRs. Matched Cox regression analyses were used to estimate associations of high CTR with mortality and hospitalization during 37 months of median follow-up. All-cause mortality occurred in 28.5% (rate 919 per 10,000 patient-years of follow-up) of patients with normal CTRs and 34.3% (rate 1,185 per 10,000 patient-years) of patients with high CTRs (hazard ratio 1.35, 95% confidence interval [CI] 1.21 to 1.51, p <0.0001). All-cause hospitalization occurred in 64.8% (rate 3,513 per 10,000 patient-years) of patients with normal CTRs and 66.2% (rate 3,932 per 10,000 patient-years) of patients with high CTRs (hazard ratio 1.10, 95% CI 1.01 to 1.20, p = 0.032). Respective hazard ratios for other outcomes were 1.48 (95% CI 1.30 to 1.68, p <0.0001) for cardiovascular mortality, 1.57 (95% CI 1.28 to 1.92, p <0.0001) for HF mortality, 1.18 (95% CI 1.08 to 1.30, p = 0.001) for cardiovascular hospitalization, and 1.27 (95% CI 1.13 to 1.44, p <0.0001) for HF hospitalization. In conclusion, a baseline CTR >0.50 was associated with increased mortality and morbidity in ambulatory patients with chronic HF. © 2008 Elsevier Inc. All rights reserved.