Background-Abnormalities in cardiac structure and function in heart failure with preserved ejection fraction may help identify patients at particularly high risk for cardiovascular morbidity and mortality. Methods and Results-Cardiac structure and function were assessed by echocardiography in a blinded core laboratory at baseline in 935 patients with heart failure with preserved ejection fraction (left ventricular ejection fraction ≥45%) enrolled in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial and related to the primary composite outcome of cardiovascular death, heart failure hospitalization, or aborted cardiac arrest, and its components. At a median follow-up of 2.9 years, 244 patients experienced the primary outcome. Left ventricular hypertrophy (adjusted hazard ratio, 1.52; 95% confidence interval, 1.16'2.00), elevated left ventricular filling pressure (E/E'; adjusted hazard ratio 1.05 per 1 integer increase; 95% confidence interval, 1.02'1.07), and higher pulmonary artery pressure assessed by the tricuspid regurgitation velocity (hazard ratio, 1.23 per 0.5 m/s increase; 95% confidence interval, 1.02'1.49) were associated with the composite outcome and heart failure hospitalization alone after adjusting for clinical and laboratory variables. The risk of adverse outcome associated with left ventricular hypertrophy was additive to the risk associated with elevated E/E'.Conclusions-Among heart failure with preserved ejection fraction patients enrolled in TOPCAT, left ventricular hypertrophy, higher left ventricular filling pressure, and higher pulmonary artery pressure were predictive of heart failure hospitalization, cardiovascular death, or aborted cardiac arrest independent of clinical and laboratory predictors. These features, both alone and in combination, identify heart failure with preserved ejection fraction patients at particularly high risk for cardiovascular morbidity and mortality.