Background and purposeThe multi‐ligand receptor for advanced glycation end‐products (RAGE, alias AGER) is suggested to contribute to the pathogenesis of vascular disease, but its potential role in stroke is unclear. The aim of this study was to investigate whether genetic variation in RAGE gene is associated with ischaemic stroke (IS).MethodsThe Sahlgrenska Academy Study on Ischaemic Stroke comprises 844 Caucasian patients with first ever (n = 732) and recurrent (n = 112) IS, and 668 Caucasian controls. Three tagSNPs were selected to capture genetic variation in the RAGE gene. IS subtypes were determined using TOAST criteria.ResultsOne SNP, rs1035798, showed significant association with the subtype of small‐vessel disease (SVD) after correction for multiple testing (OR 1.56, 95% CI 1.16–2.09), adjusted P‐value < 0.05). This association was independent of hypertension, diabetes and smoking. None of the SNPs was associated with overall IS.ConclusionIn this sample of patients with IS, genetic variation in RAGE is associated with the IS subtype SVD, but not overall IS.