Current treatment guidelines recommend anticoagulation for hypertrophic cardiomyopathy (HCM) with atrial fibrillation (AF) regardless of the CHA2DS2-VASc score. As aging and stroke risk factors (hypertension, diabetes mellitus) are confounders of ischemic stroke, young patients with a low stroke risk may not need anticoagulant treatment. This study aimed to determine the incidence of stroke and its risk factors in HCM patients with AF during a long-term follow-up. Using a national database, we retrospectively investigated 18,724 HCM patients from a systematic sample of 1,000,000 Taiwanese people between 1997 and 2013. The incidences of AF and stroke were estimated. Data were analyzed using Cox regression models. AF was identified in 598 patients (262 men, mean age 66.3±13.0 years) during a median follow-up of 7.0 years. The AF incidence in HCM patients was 5.83 per 1000 person-years, and the overall incidence of AF-associated stroke was 24.14 per 1000 person-years. The incidence of transient ischemic attack (TIA)/ischemic stroke varied from 20.41 to 60.55 per 1000 person-years, without proportionality to CHA2DS2-VASc score increase. Among patients aged <40 years, none experienced TIA/ischemic stroke. Univariate Cox regression models showed that age (p<0.001), prior TIA/ischemic stroke (p=0.02), and CHA2DS2-VASc score (p=0.003) were risk factors for TIA/ischemic stroke. Multivariate analysis indicated that age (hazard ratio 1.04, 95% confidence interval [CI] 1.02-1.06, p=0.001) and prior TIA/ischemic stroke (hazard ratio 2.82, 95% CI 1.27-6.25, p=0.011) were independently associated with TIA/ischemic stroke. Taiwanese patients with concomitant HCM and AF have a high stroke risk regardless of the CHA2DS2-VASc score. Aging is the main predictor. As the overall incidence of stroke was low in young patients, anticoagulants may not be needed in this subpopulation.