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Head and neck cancer (HNC) patients have an increased risk of carotid atherosclerosis and ischemic stroke. Apart from general risk factors such as smoking and hypertension, radiotherapy (RT) to the neck contributes to this with a subsequent relative risk of ischemic stroke of 6. The impact is a severe deterioration of the quality of life. Over the last decade, attention for long-term complications in cancer survivors has been growing. Most studies assessing RT induced carotid vasculopathy and ischemic stroke in HNC survivors were retrospective in design and mainly focused on carotid intima media thickness and ischemic stroke. However, the natural course and imaging characteristics of this RT-induced vasculopathy were not clear. Furthermore, potential clinical consequences of this carotid wall pathology, like stroke or cognitive deficits were not studied before. Therefore, we started a long-term prospective follow-up study in HNC patients treated with RT on baseline, with follow-up until seven years after RT. Study examinations include ultrasonography of the carotid wall, MRI of the carotid wall, MRI of the brain and a structured neuropsychological examination. This study showed that within the course of the first two years intima media thickness of the irradiated carotid arteries was not increased, whereas after seven years it was. The results of the MRI study were in line with the results of the ultrasonography study and showed vessel wall thickening of the irradiated carotid arteries after seven years. Furthermore, we showed that HNC patients had cognitive deficits seven years after RT, which were related to subjective complaints and fatigue and also to ischemic strokes on MRI. In fact, these cognitive deficits were multi-factorial influenced. To what extend the vascular brain lesions were a consequence of the relatively mild carotid artery wall thickening or probably more influenced by the co-occurrence of other vascular risk factors, is not clear. There are important knowledge gaps related to RT-induced carotid vasculopathy that need to be resolved in future studies. These include: 1. The relation between RT dose to the carotid arteries and incidence and severity of RT-induced carotid vasculopathy. 2. The time course of vascular changes after RT. 3. The association between cardiovascular risk factors and RT-induced carotid artery vasculopathy. 4. The relation between RT dose to the carotid arteries and ischemic brain injury