The relationship between sinusitis and ischemic stroke is unexplored. The anatomic proximity between the paranasal sinuses and the internal carotid artery suggests that inflammation of the sinuses could easily extend to the intracranial vasculature. We report 4 patients with acute ischemic stroke and extensive disease of the paranasal sinuses. All patients had large vessel stroke involving the internal carotid artery territory. All patients had extensive disease of the sphenoid and other sinuses. The sinus disease was demonstrated by magnetic resonance imaging. These case report observations suggest a relationship between inflammation of the paranasal sinuses, particularly sphenoid sinusitis, and ischemic stroke.