Beside the early detection of ischemia, there is an increasing body of evidence that diffusion-weighted imaging (DWI) can provide important information on stroke etiology. Against the background of an increased use of magnetic resonance angiography in patients being evaluated for carotid endarterectomy (CEA), the question arises if the additional performance of a DWI scan could also yield clinically relevant findings in these patients. In a prospective observational study we analysed the DWI data of 107 patients with high-grade symptomatic carotid artery disease (CAD) being evaluated for CEA. While no patient with a retinal TIA (n = 29) exhibited a DWI lesion, nineteen of the 42 patients with a hemisphere TIA and all patients with a minor stroke (n = 36) showed DWI lesion(s). In patients with TIAs the occurrence of DWI abnormalities was significantly more frequent in patients with long lasting TIAs. The majority of patients had multiple DWI lesions suggestive of acute large-artery thromboembolism as a common morphological phenotype of stroke. The finding of a similar lesion pattern in 4 patients with additional pre-existing atrial fibrillation suggested a symptomatic carotid stenosis. In contrast, unexpected bihemisphere lesions suggested cardioembolism in two patients with a normal circle of Willis and instigated thorough cardiac investigations. In both instances 24-h Holter monitoring revealed intermittent atrial fibrillation, so that a CEA was not performed. In conclusion, we demonstrate a common DWI lesion pattern in patients with symptomatic high-grade CAD eligible for CEA. In patients with known concomitant cardiac disorders the finding of this typical lesion pattern may support the diagnosis of a symptomatic CAD. In contrast, the additional performance of DWI can also reveal an unexpected cardiac source of embolism in some patients, which can substantially influence their further clinical management.