This comparative study attempts to evaluate the profile of S-100beta and Neuron-Specific Enolase (NSE), biomarkers of brain injury, in patients undergoing carotid endarterectomy (CEA) and carotid artery stenting (CAS) and to correlate this with haemodynamic and embolic events detected using trans-cranial Doppler (TCD). 52 patients with internal carotid artery stenosis requiring intervention were recruited. 24 patients underwent CAS, and 28 underwent CEA. TCD was performed peri-operatively to record mean Middle Cerebral Artery (MCA) velocity and number of High Intensity Transient Signals (HITS) in the MCA of the operated side. Serum was drawn pre-operatively and at six time points in a 48 hour post-operative period, and then assayed using automated commercial equipment. Within and between group variability in markers were assessed by Generalized Estimation Equations modelling. CAS caused more HITS (p=0.028) but less haemodynamic disturbance (p=0.0001) than CEA. Treatment modality (CAS versus CEA) had no direct effect on S-100 changes (p=0.467). NSE levels declined after revascularisation in the CAS group but not after CEA (p=0.002). S-100beta levels rose in patients who had higher numbers of HITS (p=0.002). S-100beta and NSE were not associated with changes in MCA velocity (p>0.5). S-100beta alone increased significantly at 24 hours in those patients with a post-operative neurological deficit (p=0.015). Trans-cranial Doppler findings suggest that the mechanisms of rise in S-100beta and NSE levels may differ and may be due to increased peri-operative micro-embolisation and cerebral hypoperfusion respectively. Further studies are required to assess the clinical significance of these observed changes.