Radiotherapy is extensively used in the treatment of malignant tumors of the central nervous system, but may also cause considerable morbidity and mortality, probably through damage to the remarkably vulnerable vascular system. We present two cases of infarction in the posterior cerebral vasculature related to earlier irradiation for a pineal gland tumor. Two patients were irradiated for a pineal gland tumor in young adulthood. Respectively 20 and 35 years later, they presented with a progressive neurological decline, related to early progressive atherosclerosis in the posterior cerebral vasculature. In conclusion, irradiation of the posterior cerebral territory may produce precocious atherosclerosis of posterior circulation vasculature, even decades later. When a progressive clinical decline with accumulating ischemic events is observed, together with signs of atherosclerosis, radiotherapy-related vasculopathy may be considered.