About half of all patients with heart failure (HF) have preserved left ventricular systolic function. Statins, angiotensin-converting enzyme inhibitors, and beta blockers have been shown to improve survival in patients with HF and low ejection fraction. However, no large national study has investigated these agents in patients with HF and preserved left ventricular ejection fraction. We evaluated a nationwide sample of 13,533 eligible Medicare beneficiaries aged >or=65 years who were hospitalized with a primary discharge diagnosis of HF and had chart documentation of preserved left ventricular ejection fraction between April 1998 and March 1999 or between July 2000 and June 2001. In Cox proportional hazard model accounting for demographic profile, clinical characteristics, treatments, physician specialty, and hospital characteristics, discharge statin therapy was associated with significant improvements in 1- and 3-year mortality (RR 0.69, 95% confidence interval [CI] 0.61 to 0.78; RR 0.73, 95% CI 0.68 to 0.79, respectively). Irrespective of total cholesterol level or coronary artery disease status, diabetes, hypertension, and age, statin therapy was associated with significant differences in mortality rates. Similarly, angiotensin-converting enzyme inhibitors were associated with better survival at 1 year (RR 0.88, 95% CI 0.82 to 0.95) and 3 years (RR 0.93, 95% CI 0.89 to 0.98). Beta-blocker therapy was associated with a nonsignificant trend at 1 year (RR 0.93, 95% CI 0.87 to 1.10) and significant survival benefits at 3 years (RR 0.92%, 95% CI 0.87 to 0.97). In conclusion, our data demonstrate that statins, angiotensin-converting enzyme inhibitors, and beta blockers are associated with better short- and long-term survival in patients >or=65 years with HF and preserved left ventricular ejection fraction.