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Background: Cigarette smoking predisposes individuals to the development of cardiovascular disease by promoting inflammation, vascular dysfunction, and accelerated atherosclerosis. However, the association between smoking and outcomes in HFpEF remains unclear.Objectives: To examine the relationship between smoking and outcomes in patients with HFpEF.Methods: This analysis included 1,717 (mean age=71±10 years; 50% male; 78% white) patients with HFpEF enrolled in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) Trial from the Americas. Smoking was ascertained by self-reported history and was categorized as never, former, or current. Multivariable cox regression was used to examine the risk of hospitalization, hospitalization for heart failure, death, and cardiovascular death across smoking categories.Results: There were 116 (7%), 871 (51%), and 729 (42%) patients whose smoking status was classified as current, former, or never. Current smoking was associated with an increased risk for hospitalization (never: HR=1.0; former: HR=1.14, 95%CI=0.99, 1.31; current: HR=1.38, 95%CI=1.05, 1.80), hospitalization for heart failure (never: HR=1.0; former: HR=1.25, 95%CI=0.99, 1.57; current: HR=1.68, 95%CI=1.08, 2.61), death (never: HR=1.0; former: HR=1.02, 95%CI=0.81, 1.29; current: HR=1.82, 95%CI=1.19, 2.78), and cardiovascular death (never: HR=1.0; former: HR=1.00, 95%CI=0.74, 1.35; current: HR=1.85, 95%CI=1.09, 3.24) compared with former or never smokers in a multivariable model adjusted for cardiovascular risk factors. The cumulative incidence estimates for hospitalization for heart failure across smoking categories are shown in Figure 1 (log-rank p=0.0029). Similar effect estimates were observed for smoking categories and the outcomes examined when further adjusted for quantity of cigarette use.Conclusion: Current smoking is associated an increased risk for adverse outcomes in HFpEF, including hospitalization for heart failure. Smoking cessation possibly has role to reduce the risk for hospital admission and death in these high-risk patients.