Objectives: The purpose of this study was to examine the clinical effectiveness of aldosterone antagonists in older patients with heart failure and preserved ejection fraction (HF-PEF). Background: Aldosterone antagonists improve outcomes in HF and reduced EF. However, their role in HF-PEF remains unclear. Methods: Of the 10,570 hospitalized older (≥65 years of age) HF-PEF (EF ≥40%) patients in the Medicare-linked OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure) trial, 8,013 patients had no prior aldosterone antagonist use and no current contraindications; 492 (6% of these 8,013) patients received new prescriptions for aldosterone antagonists. We assembled a matched cohort of 487 pairs of patients receiving and not receiving aldosterone antagonists, who had a similar propensity to receive these drugs and were balanced on 116 baseline characteristics. Results: Patients had a mean age of 80 years old, a mean EF of 54%, 59% were women, and 8% were African American. During 2.4 year of mean follow-up (through December 2008), the primary composite endpoint of all-cause mortality or HF hospitalization occurred in 392 (81%) and 393 (81%) patients receiving and not receiving aldosterone antagonists, respectively (hazard ratio [HR]: 0.97; 95% confidence interval [CI]: 0.84 to 1.11; p = 0.628). Aldosterone antagonists had no association with all-cause mortality (HR: 1.03; 95% CI: 0.89 to 1.20; p = 0.693) or HF hospitalization (HR: 0.88; 95% CI: 0.73 to 1.07; p = 0.188). Among 8013 prematched patients, multivariable-adjusted HR for the primary composite endpoint associated with aldosterone antagonist use was 0.93 (95% CI: 0.83 to 1.03; p = 0.144). Conclusions: In older HF-PEF patients, aldosterone antagonists had no association with clinical outcomes. Findings from the ongoing randomized controlled TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial will provide further insights into their effect in HF-PEF. © 2013 American College of Cardiology Foundation.