Asymptomatic carotid artery disease (CAD) confers a less than two per cent annual stroke risk for patients on best medical therapy, however a group of patients remain high risk for cerebral ischaemia. There is no current way of identifying such patients. This study evaluated whether carotid plaque volume (CPV) is related to cerebral ischaemia and plaque instability. Given the prominent role of antiplatelet therapy in primary and secondary prevention, antiplatelet resistance amongst patients admitted for a carotid endarterectomy (CEA) was also evaluated. Patients admitted for a primary CEA in Greater Manchester were invited to participate. Following endarterectomy, CPV was calculated using a validated water immersion technique and note made of the stenosis severity, symptom type and time from symptom. A proportion of these patients underwent transcranial Doppler (TCD) insonation of the middle cerebral artery to detect microemboli, 3D tomographic ultrasound (t-US) to measure CPV, histological analysis of the plaque along with blood sampling for antiplatelet resistance and measurement of lipoprotein-associated phospholipase A2 (Lp-PLA2), P-Selectin and high sensitive C-reactive protein (Hs-CRP). Data from a carotid surveillance clinic was explored to evaluate the effectiveness of 2D arterial duplex in carotid surveillance. Mean CPV was significantly increased in symptomatic patients and the rate at which it decreased was similar to the rate at which the benefit from CEA decreases. CPV was not related to the degree of stenosis and could be measured accurately by 3D t-US. Mean CPV was significantly increased in those patients with a histologically unstable plaque and mean Lp-PLA2 was significantly increased in those with a marked inflammatory plaque. Mean platelet aggregation was significantly increased in symptomatic patients and correlated significantly with the number of cerebral emboli. The use of 2D duplex surveillance alone is not sufficient in identifying those patients who will benefit most from CEA. CPV is a potential marker of high risk plaques with provisional results indicating it can be measured accurately using 3D t-US. Routine antiplatelet resistance testing should be considered in patients with CAD, especially those who have suffered previous CV events.