Background: Electroencephalogram-derived monitoring to assess anesthetic depth may allow more accurate hypnotic drug administration, resulting in decreased anesthetic drug consumption. The authors hypothesized that the use of M-Entropy monitoring (Datex-Ohmeda, Helsinki, Finland) is associated with reduced sevoflurane uptake (primary outcome) in patients undergoing major abdominal surgery. Methods: A total of 50 patients with an American Society of Anesthesiology score of II-III, scheduled for elective laparoscopic rectosigmoidectomy were randomized into two groups in this randomized controlled trial. In the control group, the target expiratory fraction of sevoflurane was adapted according to standard clinical practice. In the study group, the target expiratory fraction of sevoflurane was adapted to maintain state entropy values between 40 and 60. State entropy values were continuously recorded in both groups but were not available to the anesthesiologist in the control group. In both groups, patients were ventilated using the auto-control mode of the Zeus (R) (Drager, Lubeck, Germany) respirator, which allows precise measurements of sevoflurane uptake. Sufentanil was administered using a target-controlled infusion system. Results: Demographics did not differ between groups. During the anesthesia maintenance phase, state entropy values were lower in the control group than the study group (P < 0.0001). Sevoflurane uptake was higher in the control group than the study group (5.2 +/- 1.4 ml/h vs. 3.8 +/- 1.5 ml/h; P = 0.0012). Three patients in the control group developed intraoperative hypotension compared with none in the study group (P = 0.03). Conclusions: Monitoring the depth of anesthesia using M-Entropy was associated with a significant reduction in sevoflurane uptake.