Objective To study the sedative effects and safety of dexmedetomidine and midazolamfor acute exacerbate of chronic obstructive pulmonary disease ( AECOPD) underwentmechanical ventilation.Methods 68 AECOPD patients underwentmechanical ventilation were enrolled and randomly divided into adexmedetomidine group ( n =34) and a midazolam group ( n = 34) by acute physiology and chronic healthevaluation Ⅱ ( APACHEⅡ) score. The patients in the dexmedetomidine group were given a loading dose( 1 μg/kg) and then maintained with 0. 2-0. 8 mg·kg- 1 ·h- 1 . The patients in the midazolam group weregiven a loading dose ( 0. 05 mg/kg) and then maintained with 0. 06-0. 2 mg· kg- 1 · h- 1 . Sedation levelwas assessed by Ramsay score and maintained a Ramsay score of 3-4. The sedation onset time, disablesedatives wake time, duration of mechanical ventilation, extubation success rate, ICU length of stay, and 28days mortality after admission to the ICU were compared between two groups. And calmer respiratorydepression, circulatory and delirium adverse reactions incidence were also compared. Results Thedifferences in patients’age, gender, and APACHEⅡ score between two groups were not significant ( P gt;0. 05) . Compared with the midazolam group, the dexmedetomidine group had more rapid onset of sedation[ ( 49. 80 ±8. 20) s vs. ( 107. 55 ±19. 65) s, P lt;0. 01] , shorter wake-up time [ ( 18. 90 ±2. 30) min vs. ( 40. 82 ±19. 85) min, P lt;0. 01] , shorter duration of mechanical ventilation [ ( 4. 9 ±1. 6) d vs. ( 7. 8 ±2. 5) d,P lt;0. 01] , higher successful extubation rate ( 79. 41% vs. 58. 82% , P lt;0. 01) , and shorter ICUlength of stay[ ( 6. 5 ±2. 5) d vs. ( 9. 6 ±3. 4) d, P lt;0. 05] . Dexmedetomidine had lower respiratory depression rate, littleeffects on hemodynamics, lower occurrence and short duration of delirium. Conclusion It is highlyrecommended that dexmedetomidine be used for sedation in AECOPD patients with mechanical ventilation.