Concomitantly recorded Bispectral Index® (BIS) and Entropy™ values sometimes show discordant trends during general anaesthesia. Previously, no attempt had been made to discover which EEG characteristics cause discrepancies between BIS and Entropy. We compared BIS and Entropy values, and analysed the changes in the raw EEG signal during surgical anaesthesia with sevoflurane. In this prospective, open-label study, 65 patients receiving general anaesthesia with sevoflurane were enrolled. BIS, Entropy and multichannel digital EEG were recorded. Concurrent BIS and State Entropy (SE) values were selected. Whenever BIS and SE values showed ≥10-unit disagreement for ≥60 s, the raw EEG signal was analysed both in time and frequency domain. A ≥10-unit disagreement ≥60 s was detected 428 times in 51 patients. These 428 episodes accounted for 5158 (11%) out of 45 918 analysed index pairs. During EEG burst suppression, SE was higher than BIS in 35 out of 49 episodes. During delta-theta dominance, BIS was higher than SE in 141 out of 157 episodes. During alpha or beta activity, SE was higher than BIS in all 49 episodes. During electrocautery, both BIS and SE changed, sometimes in the opposite direction, but returned to baseline values after electrocautery. Electromyography caused index disagreement four times (BIS > SE). Certain specific EEG patterns, and artifacts, are associated with discrepancies between BIS and SE. Time and frequency domain analyses of the original EEG improve the interpretation of studies involving BIS, Entropy and other EEG-based indices. NCT01077674.