The indication of surgery in carotid artery disease is based on symptom status and the severity of carotid artery stenosis as measured by duplex ultrasound. The severity of stenosis itself is a poor predictor of stroke risk. An accurate predictor of stroke risk in carotid artery disease (CAD) must be identified to allow optimum clinical management. This study aimed to investigate risk factors proposed for stroke in CAD. We aimed to determine whether cerebral emboli are associated with the degree of carotid stenosis, carotid plaque volume (CPV) or resistance to platelet inhibitory therapy and to identify any circulating biomarkers that predict stroke risk in order to contribute to the development an accurate risk prediction model for CAD patients.Patients scheduled to undergo carotid endarterectomy (CEA) were recruited from the vascular department of The University Hospital of South Manchester (UHSM). Multiplate aggregometry of fresh venous blood was undertaken in 90 patients to detect platelet response to Aspirin or Clopidogrel. Transcranial Doppler ultrasound (TCD) of the middle cerebral artery was used to investigate the presence of microemboli. The severity of carotid artery stenosis was measured using duplex ultrasound preoperatively. The carotid plaque volume (CPV) of the endarterectomy specimen was measured using a modified Archimedes technique. Metabolomic analysis of plasma samples was used to identify any biomarkers present at levels significantly different between asymptomatic and symptomatic groups. Mean residual platelet aggregation despite antiplatelet therapy was 28.5 ± 2.8 AU in asymptomatic patients compared with 55.5 ± 3 AU in symptomatic patients (p=0.01). Resistant patients had more frequent MES at a mean rate of 6.6 ± 2.8 /hour compared with 1.8 ± 1.7 /hour in non-resistant patients (p=0.003). There was a significant association between the frequency of MES and residual platelet aggregation (p=0.002). No correlation between severity of stenosis and MES could be identified (p=0.7) but CPV significantly related to MES (p=0.03). No significant plasma biomarker was identified but metabolomic investigation of plasma proved to be a successful method of analysis.It is clear that carotid stenosis alone is a poor predictor of stroke risk in CAD. Antiplatelet resistance and CPV were associated with symptom status and cerebral emboli in CAD and may therefore predict stroke risk. Further research is needed to identify significant plasma biomarkers.