Background: The impact of gender on major natural history endpoints in heart failure (HF) has not been examined in a propensity-matched study. Methods: Of the 7788 chronic systolic and diastolic HF patients in the Digitalis Investigation Group trial 1926 were women. Propensity scores for female gender were used to assemble a cohort of 1669 pairs of men and women who were well-balanced on 32 measured baseline characteristics. Matched hazard ratios (HR) and 95% confidence intervals (CI) for outcomes associated with female gender were calculated using stratified Cox regression models. Results: All-cause mortality occurred in 36% (rate, 1256/10,000 person-years) and 30% (rate, 1008/10,000 person-years) of matched men and women respectively during 5 years of follow up (HR when women were compared with men, 0.82, 95% CI, 0.72-0.94, P = 0.004). Female gender was also associated with reduced cardiovascular mortality (matched HR, 0.85; 95% CI, 0.73-0.99, P = 0.037) and a trend toward reduced non-cardiovascular mortality (matched HR, 0.73; 95% CI, 0.53-1.00; P = 0.053). All-cause hospitalization occurred in 67% (rate, 4003/10,000 person-years) and 65% (rate, 3762/10,000 person-years) matched male and female patients respectively (HR for women, 1.03, 95% CI, 0.93-1.15, P = 0.538). Female gender was not associated with cardiovascular or HF hospitalization but was associated with hospitalization due to unstable angina pectoris (matched HR, 1.38; 95%CI, 1.11-1.72; P = 0.003) and stroke (matched HR, 0.65; 95%CI, 0.46-0.92; P = 0.014). Conclusions: In patients with chronic HF, female gender has a significant independent association with improved survival but has no association with all-cause, cardiovascular, or HF hospitalizations.