Background Recent genomewide association studies have revealed an association between two single nucleotide polymorphisms, rs11833579 and rs12425791, and ischemic stroke. Aim To gain more insight in pathophysiological mechanisms underlying the found associations by exploring relationships between these single nucleotide polymorphisms and clinical and radiological characteristics of patients with cerebral ischemia. Methods Our cohort consisted of 660 Caucasian patients with cerebral ischemia; from all patients detailed clinical and radiological data were available. Etiologic subtype of cerebral ischemia was determined according to the TOAST classification and an alternative classification. We studied associations between risk alleles and etiologic subtype, duration of ischemia, occurrence of multiple events, functional outcome and findings on CT-angiography by means of logistic regression analysis. Results The risk allele of rs11833579 was associated with an atherothrombotic etiology of cerebral ischemia, but not with other etiologic subtypes. Risk alleles of both single nucleotide polymorphisms were related to events of shorter duration (<24 h), the risk allele of rs11833579 with occurrence of multiple events. There was no association between single nucleotide polymorphism and clinical outcome. Both single nucleotide polymorphisms were associated with presence of stenotic calcifications and stenosis >30% in a symptomatic artery on CT-angiography. Conclusions This is the first study to show an association of rs11833579 with multiple episodes of cerebral ischemia of atherothrombotic origin, and of rs11833579 and rs12425791 with short duration of ischemia. Also, we found an association of both single nucleotide polymorphisms with atherosclerotic lesions in the extracranial vessels on CT-angiography. Together this suggests a relationship between the two single nucleotide polymorphisms and large artery pathology.