Increased incidence of postoperative cognitive dysfunction (POCD) is observed in elderly patients underwent intravenous anesthesia (TIVA) with endotracheal intubation. Modulation of anesthetics compatibility may reduce the severity of POCD. Elderly patients scheduled for TIVA with endotracheal intubation were randomly divided into the control group (1.00?2.00 mg/kg propofol) and the etomidate and propofol combination group (1.00?2.00 mg/kg propofol and 0.30 mg/kg etomidate). Serum cortisol, S100?, and neuron-specific enolase (NSE), interleukin (IL)-6, and IL-10 were monitored during or after the operation. Mini-mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were utilized to assess the severity of POCD. 63 elderly patients in the etomidate and propofol combination group and 60 patients in the control group were enrolled, and there was no significant difference in gender, American Society of Anesthesiologists (ASA) physical status, surgical specialty, intraoperative blood loss, and operation time between the two groups. Significantly increased serum cortisol, S100?, NSE, IL-6, and reduced MMSE and MoCA scores were detected in the control group at different time points after the operation (0-72 h post operation) when compared to those before the operation. Similar trends for these observed factors were found in the etomidate and propofol combination group. In addition, the etomidate and propofol combination group showed better effects in reducing the serum levels of cortisol, S100?, NSE, IL-6, and increasing the MMSE and MoCA scores when compared to the control group. The present study demonstrates that the combination of propofol with etomidate could alleviate POCD in elderly patients underwent TIVA with endotracheal intubation anesthesia.

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