Background: The Bispectral Index (BIS) is an electroencephalogram-derived measure of anesthetic depth. A closed-loop anesthesia system was built using BIS as the control variable, a proportional–integral–differential control algorithm, and a propofol target-controlled infusion system as the control actuator. Closed-loop performance was assessed in 10 adult patients. Methods: Ten adult patients scheduled to undergo elective hip or knee surgery were enrolled. An epidural cannula was inserted, and 0.5% bupivacaine was used to provide anesthesia to T8 before general anesthesia was induced using the propofol target-controlled infusion system under manual control. After the start of surgery, when anesthesia was clinically adequate, automatic control of anesthesia was commenced using the BIS as the control variable. Adequacy of anesthesia during closed-loop control was assessed clinically and by calculating the median performance error, the median absolute performance error, and the mean offset of the control variable. Results: The median performance error and the median absolute performance error were 2.2 and 8.0%, respectively. Mean offset of the BIS from the set point was 0.9. Cardiovascular parameters were stable during closed-loop control. Operating conditions were adequate in all patients but one, who began moving after 45 min of stable anesthesia. No patients reported awareness or recall of intraoperative events. In three patients, there was oscillation of the measured BIS around the set point. Conclusions: The system was able to provide clinically adequate anesthesia in 9 of 10 patients. Further studies are required to determine whether control performance can be improved by alterations to the gain factors or by using an effect site–targeted, target-controlled infusion propofol system.