Optimal therapy for diastolic heart failure (DHF), the most common form of heart failure in older persons, is unclear. To determine the effect of aldosterone antagonism in DHF, the authors conducted an open-label preliminary trial of spironolactone 25 mg/d in 11 women with DHF. Cardiopulmonary exercise testing, Doppler echocardiography, and a quality-of-life survey were administered at baseline and after 4 months. Peak exercise VO(2) increased by 8.3% (P=.001), the ratio of Doppler diastolic early filling velocity to mitral annulus velocity decreased by 25% (P=.02), quality-of-life score improved by 21% (P=.16 for trend), and median New York Heart Association class improved from class III to class II (P=.004). Findings from this preliminary study confirm the role of aldosterone in the pathophysiology of DHF and suggest that aldosterone antagonism may benefit such patients. These hypotheses are currently being tested in two separated National Institutes of Health-funded, randomized trials, the Spironolactone for Failure in the Elderly (SPIFFIE) and the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trials.