OBJECTIVE： To compare the sedative effects of dexmedetomidine and midazolam in patients with comprehensive ICU mechanical ventilation. METHODS： 74 patients in ICU were randomly divided into dexmedetomidine group （37 cases） and midazolam group （37 cases）. Based on mechanical ventilation，dexmedetomidine group received 200 μg Dexmedetomidine injection， dissolving in 48 ml 0.9％ Sodium chloride injection， pumped by 1 μg/kg within 30 min， then adjusted to 0.2-0.7 μg/（kg·h） by micropump.  Midazolam group received 30 mg Midazolam injection， dissolving in 44 ml 0.9％ Sodium chloride injection， pumped by 0.05 mg/kg within 15 min， then adjusted to 0.04-0.20 mg/（kg·h） by micropump. The sedative effects， clinical indicators （weaning time， extubation time， time of mechanical ventilation， ICU hospitalization time） and the incidence of adverse reactions in 2 groups were observed. RESULTS： There was no significant difference in the sedative effects （P＞0.05）； weaning time， extubation time， and ICU hospitalization time in dexmedetomidine group were significantly shorter than midazolam group， the differences were statistically significant （P＜0.05）； the incidence of total adverse reactions in dexmedetomidine group was significantly lower than midazolam group， the difference was statistically significant （P＜0.05）. CONCLUSIONS： Dexmedetomidine show similar sedative effects with midazolam in patients with comprehensive ICU mechanical ventilation， shorter weaning time， extubation time， ICU hospitalization time， and lower incidence of total adverse reactions than midazolam.