Smoking is an important risk factor in the development of heart failure with preserved ejection (HFpEF), and prior reports have identified smoking as a significant predictor of death in this population. However, the relationship between smoking and heart failure-specific outcomes has not been examined in patients with HFpEF. 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 for heart failure, death, and cardiovascular death across smoking categories. There were 116 (7%) current, 871 (51%) former, and 729 (42%) never smokers in this analysis. Current smoking was associated with an increased risk for 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. A similar increased risk for hospitalization for heart failure (former: HR=1.0; current: HR=1.54, 95%CI=1.01, 2.36), death (former: HR=1.0; current: HR=1.81, 95%CI=1.19, 2.75), and cardiovascular death (former: HR=1.0; current: HR=1.76, 95%CI=1.04, 2.98) was observed for current smokers when we limited the analysis to those with a history of smoking. In conclusion, current smoking is associated an increased risk for adverse outcomes in HFpEF, including hospitalization for heart failure. Smoking cessation strategies possibly have a role to reduce the risk for adverse cardiovascular outcomes in patients with HFpEF.