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Elderly patients are more prone than younger patients to develop cerebral desaturation because of the reduced physiologic reserve that accompanies aging. To evaluate whether monitoring cerebral oxygen saturation (rSO2) minimizes intraoperative cerebral desaturation, we prospectively monitored rSO2 in 122 elderly patients undergoing major abdominal surgery with general anesthesia. Patients were randomly allocated to an intervention group (the monitor was visible and rSO2 was maintained at ≥75% of preinduction values; n = 56) or a control group (the monitor was blinded and anesthesia was managed routinely; n = 66). Cerebral desaturation (rSO2 reduction <75% of baseline) was observed in 11 patients of the treatment group (20%) and 15 patients of the control group (23%) (P = 0.82). Mean (95% confidence intervals) values of mean rSO2 were higher (66% [64%–68%]) and the area under the curve below 75% of baseline (AUCrSO22< 75% of baseline) was lower (0.4 min% [0.1–0.8 min%]) in patients of the treatment group than in patients of the control group (61% [59%–63%] and 80 min% [2–144 min%], respectively; P = 0.002 and P = 0.017). When considering only patients developing intraoperative cerebral desaturation, a lower Mini Mental State Elimination (MMSE) score was observed at the seventh postoperative day in the control group (26 [25–30]) than in the treatment group (28 [26–30]) (P = 0.02), with a significant correlation between the AUCrSO2 < 75% of baseline and postoperative decrease in MMSE score from preoperative values (r2= 0.25, P = 0.01). Patients of the control group with intraoperative cerebral desaturation also experienced a longer time to postanesthesia care unit (PACU) discharge (47 min [13–56 min]) and longer hospital stay (24 days [7–53] days) compared with patients of the treatment group (25 min [15–35 min] and 10 days [7–23 days], respectively; P = 0.01 and P = 0.007). Using rSO2 monitoring to manage anesthesia in elderly patients undergoing major abdominal surgery reduces the potential exposure of the brain to hypoxia; this might be associated with decreased effects on cognitive function and shorter PACU and hospital stay.