Background: The term “postoperative cognitive dysfunction (POCD) syndrome” is applied to an impairment of higher mental functions that may occur postoperatively and are related to the surgery and anesthesia. Medical and social impact of POCD is undoubted due to its high incidence (up to 30% after non-cardiac surgery), high expenses related to the restoration of cognitive functions, as well as the need in social adaptation of the patients. Aim: To decrease the risk of POCD after subtotal hysterectomy through optimization of anesthesiological care. Materials and methods: This prospective, single blind study performed from May 2016 to October 2017 included 67 middle-aged women with large uterine myomas or multimodal myomas, who underwent subtotal hysterectomy (through laparotomic Pfannenstiel incision) under general anesthesia. The patients were divided into two groups depending on the anesthesia method. The patients from group 1 (n = 35) were operated under inhalational sevoflurane anesthesia with micro-bolus fentanyl infusion (100 to 300 µg/h). In the patients from group 2 (n = 32), micro-boluses of dexmedetomidine were started 15 minutes before intubation at doses of 0.4 to 1.1 µg/kg/h, ending at the time of the wound closure. Cognitive functions were assessed with MMSE (Mini Mental State Examination) and МОСА (Montreal Cognitive Assessment) scales preoperatively and in the early postoperative period (at days 1 and 5). Results: There was a signifcant difference in cognitive functions between the groups at days 1 and 5 after surgery. In the dexmedetomidine group, the cognitive parameters were signifcantly better: median MOCA score was 26 vs 25 (p < 0.001) at day 1 and 27 vs 26 (p < 0.001) at day 5. MMSE scores at day 1 were 27 vs 25 (p < 0.005) and at day 5, 28 vs 27 (p < 0.001). The group 2 patients also had lower opioid requirements (p < 0.001). Conclusion: The use of dexmedetomidine for hysterectomy under inhalational sevoflurane anesthesia allows for reduction of postoperative cognitive impairment in the early postoperative period.