Atherosclerosis causes plaque to form in the carotid arteries, usually at the fork where the common carotid artery divides into the internal and external carotid artery. The plaque can build up in the inner surface of the artery (lumen), and narrow or constrict the artery. Pieces of the plaque, called emboli, can break off (i.e. embolize) and travel up the internal carotid artery to the brain, where it blocks circulation, and can cause death of the brain tissue.

Sometimes the plaque causes symptoms first. The symptoms are temporary or transitory strokes, known as transient ischemic attacks (TIAs). By definition, TIAs last less than 24 hours; after 24 hours they are called strokes. Symptomatic stenosis has a high risk of stroke within the next 2 days. National Institute for Health and Clinical Excellence (NICE) guidelines recommend that patients with moderate to severe (50-99% blockage) stenosis, and symptoms, should have "urgent" endarterectomy within 2 weeks.

When the plaque doesn't cause symptoms, patients are still at higher risk of stroke than the general population, but not as high as patients with symptomatic stenosis. The incidence of stroke, including fatal stroke, is 1–2% per year. The surgical mortality of endarterectomy ranges from 1–2% to as much as 10%. Two large randomized clinical trials have demonstrated that carotid surgery done with a 30-day stroke and death risk of 3% or less will benefit asymptomatic patients with ≥60% stenosis who are expected to live at least 5 years after surgery. Surgeons are divided over whether asymptomatic patients should be treated with medication alone or should have surgery.