Objective To investigate the effect of midazolam and fentanyl on etomidate-induced myoclonus. Methods A total of 128 patients scheduled for surgery under genaral anesthesia were randomly divided into 5 groups according to the different sequence and dose of anesthetics during anesthesia induction. Midazolam 0. 05 mg/kg, etomidate 0. 25 mg/kg and fentanyl 3μg/kg was used in group Ⅰ, fentanyl 3 μg/kg, etomidate 0. 25 mg/kg, midazolam 0.05 rng/kg in group H,midazoIam 0. 05 mg/kg, fentanyl 3 μg/kg, etomidate 0. 25 mg/kg in group Ⅲ, midazolam 0. 08 mg/kg, etomidate 0. 25 mg/kg, fentanyl 3 μg/kg in group Ⅳ, etomidate 0. 25 mg/kg, midazolam 0. 05 mg/kg, fentanyl 3 μg/kg in group Ⅴ as the control After the injection of etomidate, the scales and positive incidences of myoclonus were observed within 2 minutes. Results The positive incidences of myoclonus were 68. 18% in group Ⅰ, 41.67% in group Ⅱ, 21.88% in group Ⅲ, 21.74% in group Ⅳ, and 59. 26% in group Ⅴ, respectively. Compared with group Ⅴ, groups of Ⅲ and Ⅳ had lower positive incidences and scales (P < 0. 05), whereas groups of Ⅰ and Ⅱ had no statistical changes in positive incidences and scales. Conclusion Using midazolarn, fentanyl, and etomidate consequently may reduce the occurrence of etornidate-induced myoclonus during anesthesia induction.