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Objectives: We sought to determine whether hormone replacement therapy (HRT) is associated with an improved prognosis in women with advanced heart failure (HF) and systolic dysfunction., Background: There are about two million postmenopausal women in the U.S. with HF. However, limited data are available to assess the effects of HRT on survival in this large group of patients., Methods: A retrospective analysis of women age 50 years and over entered into the Beta-Blocker Evaluation of Survival Trial (BEST) was conducted using Cox regression analysis comparing survival in HRT users and non-users after correcting for baseline variables known to predict survival in women with HF and systolic dysfunction., Results: In 493 women age 50 years and older, HRT was associated with a significant reduction in mortality-21% mortality in HRT users and 34% in non-users (p = 0.025). Multivariate analysis demonstrated a hazard ratio for mortality of 0.6 (95% confidence interval = 0.36 to 0.97) (p = 0.039) for HRT users. The benefits of HRT were noted only in women with a nonischemic etiology of HF (n = 237)., Conclusions: Hormone replacement therapy is associated with a marked improvement in survival in postmenopausal women with advanced HF. A prospective, randomized trial of HRT should be performed in this large group of patients.