Emerging evidence indicates sinus node dysfunction (SND) may be an important marker of a biatrial myopathy. However, the relative risk of ischemic stroke in isolated SND has not been clearly delineated in comparative prospective studies. This study examined the association between SND (with and without concomitant atrial fibrillation [AF]) and ischemic stroke (IS) in the United Kingdom Biobank (UKB). The UKB is a prospective, population-based cohort of >500,000 individuals aged 40-69 years recruited across the UK between 2006 and 2010, with follow-up extending beyond 10 years. Incident health events were longitudinally tracked through electronic health record linkages with hospital admissions, primary care records and death registration data using ICD-10 coding. Individuals with SND, AF or both were identified. Patients with prosthetic heart valves, rheumatic mitral valve diseases, mitral stenosis and prior IS were excluded. The primary endpoint was time to IS. Of the 451,493 participants (median age 57 years, 44.2% male) included in this study: 593 had isolated SND, 955 had combined SND and AF, 37,065 had isolated AF and 412,880 comprised controls with neither SND nor AF. During median follow-up of 13.2 years, yearly IS incidence was 0.37%, 0.60%, 0.59% and 0.10% in these groups, respectively. In multivariable competing-risk regression modelling accounting for death, isolated SND conferred a significantly increased risk of IS compared to controls (sub-distribution hazard ratio [SHR] 2.28; 95% CI, 1.57-3.31; p<0.001). Participants with AF and SND had similar risk of IS, compared to those with isolated AF (SHR 1.07; 95% CI, 0.84-1.37; p=0.58). SND is an independent risk marker for development of IS in individuals without AF. This provides further evidence of SND being an electrical marker of a biatrial myopathy.