Heart failure with preserved ejection fraction (HFpEF) is associated with an increased risk of stroke.This study sought to determine whether the Essen Stroke Risk Score (ESRS) could predict the risks of adjudicated clinical outcomes in patients with Heart failure with preserved ejection fraction (HFpEF) from the TOPCAT trial. Of 3,441 HFpEF patients with a mean follow-up of 3.3 years, the risk of stroke ranged from 0.32% per year at an ESRS of 1-2 points to 1.71% per year at a score of ≥6 points. Each point increase in ESRS was associated with increased risks of stroke (HR=1.33 [95% CI 1.16-1.53]) with a C-index of 0.68, as well as myocardial infarction (HR=1.60 [95% CI 1.40-1.83]; C-index, 0.75), HF hospitalization (HR=1.30 [95% CI 1.20-1.41]; C-index, 0.71), any hospitalization (HR=1.20, 95% CI 1.15-1.26; C-index, 0.68), cardiovascular death (HR=1.32 [95% CI 1.20-1.44]; C-index, 0.68), and all-cause death (HR=1.37, [95% CI 1.28-1.48]; C-index, 0.68). The calibration curve showed that the ESRS had an adequate agreement between predicted and observed stroke risk. The ESRS had similar predictive abilities compared to the R2CHADS2, CHADS2, or CHA2DS2-VASC stroke scores as assessed by non-significant Z-statistics, NRI and IDI values.The ESRS had modest discriminatory abilities for predicting stroke as well as other adverse outcomes including myocardial infarction, hospitalization, and death in HFpEF patients. Furthermore, ESRS might have improvement in clinical usefulness compared with other scores in patients at high risk for stroke.