Background Ischemic stroke is a common complication in patients with hypertrophic cardiomyopathy (HCM) (1). Although atrial fibrillation (AF) is a well-established risk factor for ischemic stroke in HCM, the risk of ischemic stroke in patients with HCM without documented AF is less recognized (1, 2). This study aimed to determine the risk of ischemic stroke and identify its risk factors in patients with HCM without documented AF. Methods This nationwide population-based cohort study used the Korean National Health Insurance database. After excluding patients with a prior history of AF, thromboembolic events, cancer, or the use of anticoagulants, we identified 8,328 HCM patients without documented AF and 1:2 propensity score-matched 16,656 non-HCM controls. The clinical outcome was an incident ischemic stroke. Results During a mean follow-up of approximately 6 years, ischemic stroke occurred in 328/8,328 (3.9%) patients with HCM and 443/16,656 (2.7%) controls. Among individuals who developed ischemic stroke, the proportion of AF concomitantly detected accounted for 26.5% (87/328) and 5.8% (26/443) in the HCM and control groups, respectively. The overall incidence of ischemic stroke was 0.716/100 person-years in the HCM group, which was significantly higher than that in the control group (0.44/100 person-years) (HR 1.643; 95% CI, 1.424–1.895; P<0.001, Figure 1). The subgroup analysis according to age, sex, and comorbidities (chronic heart failure, hypertension, dyslipidemia, and vascular disease) consistently demonstrated a higher risk of ischemic stroke in the HCM group (P for interaction >0.05). In the HCM group, age ≥65 years (adjusted hazard ratio [HR] 2.741; 95% confidence interval [CI], 2.156–3.486; P<0.001) and chronic heart failure (adjusted HR 1.748; 95% CI, 1.101–2.745; P=0.018) were independent risk factors for ischemic stroke. Overall incidence was 1.360/100 in patients with HCM aged ≥65 and 2.315/100 person-years years in those with chronic heart failure, respectively. Also, compared to controls aged <65 years and without CHF, adjusted HR for ischemic stroke was 4.756 (95% CI 3.807–5.867) in patients with HCM aged ≥65 years and 2.539 (95% CI 1.638–3.936) in those with CHF, respectively (Figure 2). Conclusions Patients with HCM without documented AF are at a higher risk of ischemic stroke than the propensity score-matched general population. Age ≥65 years and chronic heart failure are two strong independent risk factors for ischemic stroke in this population. Funding Acknowledgement Type of funding sources: None.