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This report describes a closed-loop titration of propofol target control infusion based on a proportional-differential algorithm guided by the Bispectral Index (BIS) allowing induction and maintenance of general anesthesia and compares this to manual propofol target control infusion.One hundred sixty-four patients scheduled to undergo elective minor or major surgery were prospectively randomized in a multicenter study into the closed-loop (n = 83) or manual target control infusion group (n = 81). The goal was to reach a BIS target of 50 during induction and to maintain it between 40 and 60 during maintenance. For both groups, remifentanil target control infusion was adjusted manually, and ventilation was without nitrous oxide.Closed-loop control was able to provide anesthesia induction and maintenance for all patients. During induction, propofol consumption was lower in the closed-loop group (1.4 ± 0.5 vs. 1.8 ± 0.6 mg/kg; P < 0.0001), but the duration was longer (320 ± 125 vs. 271 ± 120 s; P < 0.0002). Adequate anesthesia maintenance, defined as the BIS in the range of 40–60, was significantly higher in the closed-loop group (89 ± 9 vs. 70 ± 21%; P < 0.0001), with a decrease of the occurrence of BIS less than 40 (8 ± 8 vs. 26 ± 22%; P < 0.0001). Time from discontinuation of propofol infusion to tracheal extubation was shorter in the closed-loop group (7 ± 4 vs. 10 ± 7 min; P < 0.017). Unwanted somatic events and hemodynamic instability were similar.Automatic control of consciousness using the BIS is clinically feasible and outperforms manual control.