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This study aimed at investigating the Bispectral Index (BIS) profile during carotid cross clamping (CXC). The study involved a pilot group of 10 patients undergoing routine carotid endarterectomy with shunt insertion under total intravenous anesthesia, and a study group of 26 additional patients. In all patients, rates of propofol and remifentanil providing a steady-state level of hypnosis (BIS: 40-60) were maintained constant throughout a recording period ranging from 3 minutes before CXC to shunt insertion. BIS was recorded throughout this period and the internal carotid backflow observed at the time of shunt insertion was graded as good, moderate, or poor. In addition, A-Line Autoregressive Index (AAI) and processed electroencephalogram (EEG) parameters were recorded in patients of the study group. All parameters were averaged over 1 minute before CXC, at CXC, 1, 2, and 3 minutes after CXC, and at shunt insertion. Statistical analysis was performed using chi2, Friedman, and Spearman correlation tests. For technical reasons, reliable AAI, BIS monitor-derived, and other processed EEG data were obtained in 24, 25, and 18 patients of the study group, respectively. During the first 3 minutes after CXC, BIS increased over 60 [68.8 (6.1)] in 47%, decreased below 40 [34.9 (4.4)] in 25%, and remained in the 40 to 60 range in 28% of all recruited patients. A BIS increase was more frequently observed in patients with moderate or poor than in those with good internal carotid backflow (78, 67, and 29%, respectively). It was significantly correlated to an increase in AAI and EEG amplitude, a decrease in EEG suppression ratio, and a shorter time between induction of anesthesia and CXC. A BIS decrease was significantly correlated to an increase in suppression ratio and a longer time between induction and CXC. In conclusion, during CXC under a constant level of intravenous anesthesia, BIS may increase, decrease, or remain unchanged. The paradoxical BIS increase could be related to borderline ischemia, a change in brain anesthetic agent concentration, or a change in the nociceptive-antinociceptive balance associated with a CXC-elicited painful stimulation. Caution should be used when interpreting BIS value during CXC.