Background: The association between higher New York Heart Association (NYHA) class and outcomes in patients with heart failure and preserved systolic function is not well known. Methods: We performed a retrospective follow-up study of 988 patients with heart failure with ejection fraction >45% who participated in the DIG trial. Using Cox proportional hazard models, we estimated risks and all-cause mortality, heart failure mortality, all-cause hospitalization, and hospitalization due to worsening heart failure during a median follow-up of 38.5 months. Results: Patients had a median age of 68 years; 41.2% were women and 13.9%, nonwhites. Overall, 23.4% of patients died, and 19.9% were hospitalized because of worsening heart failure. Proportion of patients with NYHA classes I, II, III, and IV were 19.9%, 58.0%, 20.9%, and 1.2%, respectively, and 14.7%, 21.1%, 35.9%, and 58.3%, respectively, died of all causes (P < .001 for trend). Respective rates for heart failure-related hospitalizations were 14.2%, 17.1%, 32.5%, and 33.3% (P < .001 for trend). Compared with NYHA class I patients, adjusted hazard ratios (HRs) for all-cause mortality for class II, III, and IV patients were 1.54 (95% CI 1.02-2.32, P = .042), 2.56 (95% CI 1.64-24.01, P < .001), and 8.46 (95% CI 3.57-20.03, P < .001), respectively. Respective adjusted HRs (95% CI) for hospitalization due to heart failure for class II, III, and IV patients were 1.16 (0.76-1.77) (P = .502), 2.27 (1.45-3.56) (P < .001), and 3.71 (1.25-11.02) (P = 018). New York Heart Association classes II through IV were also associated with higher risk of all-cause hospitalization. Conclusion: Higher NYHA classes were associated with poorer outcomes in patients with heart failure and preserved systolic function. © 2006, Mosby, Inc. All rights reserved.