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During induction of general anesthesia, proper mask ventilation is crucial for supplying sufficient oxygen to unconscious patients. Midazolam has a relaxing effect on airway muscles. We hypothesized that sedative premedication with midazolam would facilitate mask ventilation during anesthetic induction.Patients undergoing elective surgery under general anesthesia were randomized into 2 groups. The midazolam group received midazolam premedication at the reception area, 3 minutes before transfer to the operating room. Patients in the control group were treated with normal saline as a placebo. The primary outcome was difficulty of mask ventilation during induction, as evaluated using the Warters scales.A total of 97 patients completed the analysis: 49 in the control group and 48 in the midazolam group. The patients in the midazolam group showed a significantly lower mask ventilation difficulty score on the Warters scale than that of the control group (mean [standard deviation], 0.92 [1.13] vs 0.19 [0.57]; estimated difference [95% confidence interval], 0.73 [0.37−1.09]; P < .001). The incidence of difficult mask ventilation (≥2 Warters scale) was significantly lower in the midazolam group than in the control group (risk ratio [95% confidence interval], 0.15 [0.03−0.72]; P = .015).This randomized clinical trial demonstrated that midazolam premedication enhanced mask ventilation during induction of general anesthesia.