Background. The mechanism of stroke in beta-thalassemia was reported previously as cardioembolic and hypercoagulable state. However, there is no report of watershed infarct in beta-thalassemia anemia.Method. We present an adultβ-thalassemia major patient with manifest asymptomatic chronic left carotid occlusion who suffered watershed infarct.Result. In the presence of asymptomatic chronic left internal carotid occlusion, we assumed that severe anemia (hemoglobin = 3) at admission leads to watershed infarct.Conclusion. Watershed infarct seems to be the cause of stroke in cases ofβ-thalassemia major with severe anemia. Blood transfusion can be applied in the setting of acute brain ischemia in such high risk patients.