OBJECTIVE: To prospectively compare the use of the cerebral blood flow monitor (c-FLOW) and transcranial Doppler (TCD) as 2 techniques for assessing brain perfusion during carotid endarterectomy. METHODS: This was a prospective, single-center, observational study. All patients were monitored using c-FLOW and TCD during the operation. Changes from baseline values of cerebral blood flow index and blood flow velocity of middle cerebral artery (V-MCA) were recorded following carotid artery clamping and unclamping. The correlation analysis was conducted for c-FLOW and TCD monitoring values. RESULTS: Seventy-three consecutive patients were enrolled from August 2015 to March 2016. No death or stroke occurred during the postoperative hospitalization. Fresh infarction was identified on magnetic resonance imaging in 17 patients. Ten patients showed a significant decrease of V-MCA following carotid clamping. A shunt was placed for only 4. The Pearson correlation index between CFI and V-MCA was 0.647 (P < 0.001). A cut-off of 21% decrease of CFI was proposed as optimal to detect intraoperative hypoperfusion. Seven patients were diagnosed as having hyperperfusion by TCD monitoring. The Pearson correlation index between CFI and V-MCA was 0.286 (P = 0.014). A cut-off of 15% increase of CFI following carotid unclamping was suggested as optimal to detect the postoperative hyperperfusion. CONCLUSIONS: c-FLOW could continuously and non-invasively monitor the cerebral blood flow in real-time during carotid endarterectomy and effectively detect the intraoperative hypoperfusion and postoperative hyperperfusion as defined by TCD so that it may serve as a favorable modality in future intraoperative monitoring.