Background: Although high resting heart rate (RHR) is known to be associated with an increased risk of mortality and hospital admission in patients with heart failure, the relationship between RHR and ischemic stroke remains unclear. This study is aimed at investigating the relationship between RHR and ischemic stroke in patients with heart failure in sinus rhythm. Methods: We examined 2,060 patients with systolic heart failure in sinus rhythm from the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial. RHR was determined from baseline electrocardiogram, and was examined as both a continuous variable and a categorical variable using quartiles. Ischemic strokes were identified during follow-up and adjudicated by physician review. Results: During 3.5 ± 1.8 years of follow-up, 77 patients (5.3% from Kaplan-Meier [KM] curve) experienced an ischemic stroke. The highest incidence of ischemic stroke (21/503 [KM 6.9%]) was observed in the lowest RHR quartile (RHR <64 beats/min) compared to other groups; 22/573 (KM 5.3%) in 64-70 beats/min, 13/465 (KM 3.5%) in 71-79 beats/min, and 21/519 (KM 5.4%) in RHR >79 beats/min (p = 0.693). Multivariable Cox proportional hazards analysis revealed that RHR was significantly associated with ischemic stroke (hazard ratio per unit decrease: 1.07, 95% CI 1.02-1.13, when RHR <64/beats/min; p = 0.038), along with a history of stroke or transient ischemic attack and left ventricular ejection fraction. Conclusions: In contrast to its beneficial effect on mortality and hospital re-admissions, lower RHR may increase the risk of ischemic stroke in patients with systolic heart failure in sinus rhythm.