Many well-controlled clinical studies have shown that BIS-guided anesthesia could prevent intraoperative awareness and improve postoperative morbidity and mortality, by optimizing the amount of volatile anesthetics administered to patients. However, we questioned if the previously reported advantages of BIS-guided anesthesia in controlled studies would still apply in real-world settings. This retrospective study based on real-world settings clarified the role of BIS-guided anesthesia in reducing anesthetic consumption. We obtained anesthesia records from an electronic database of a medical center in southern Taiwan. A total of 6,713 cases were enrolled, where 1,324 cases receiving sevoflurane underwent BIS-guided anesthesia and 378 received desflurane; further, 3,819 receiving sevoflurane underwent standard anesthesia practice and 1,192 cases received desflurane. The median (25-75% interquartile values) of the average hourly consumption of sevoflurane or desflurane decreased significantly under BIS-guided anesthesia [10.5 (8.7-13.0) mL/h and 17.4 (13.7-21.1) mL/h, respectively] compared to that under standard anesthesia practice [11.4 (9.0-14.5) mL/h, and 20.2 (15.8-25.0), mL/h, respectively]. Furthermore, the average hourly consumption of these two volatile anesthetics varied inversely with age and anesthesia time in both groups. A significant reduction was found in the hourly consumption of volatile anesthetics in patients under BIS-guided anesthesia compared to standard anesthesia practice in different age groups or different anesthesia time. We concluded that BIS-guided anesthesia could reduce consumption of volatile anesthetics in real-world settings as well.