Background: Sedation in the intensive care unit Patients is assumed to reduce discomfort from care interventions, increase tolerance of mechanical ventilation, prevent accidental removal of instrumentation, and reduce metabolic demands during cardiovascular and respiratory instability. Aim of the Work: The aim of the work was to evaluate the use of dexmedetomedine as a sedative to facilitate weaning from mechanical ventilation and extubation, so decrease the incidence of reintubation, ventilator complications and decrease the ICU cost and stay. Patients and Methods: This was a controlled randomized prospective clinical trial carried out at Ain-Shams University Hospitals. After approval of institutional ethical committee, the study included 90 adult postoperative patients and requiring postoperative mechanical ventilation in the surgical ICU for maximum duration of 48 hours postoperatively. Results: As regard to time to extubation, results of the current study showed a highly statistically significant difference between three groups regarding time to extubation (hr) when p-value was < 0.001. Conclusion: dexmedetomidine has clinically relevant benefits compared to midazolam and propofol in facilitating extubation because of its shorter time to extubation, more hemodynamic stability, easy arousability and lack of respiratory depression; hence, it can be used as an effective, and safe sedative agent to facilitate extubation in ICUs and decreasing ICU length of stay.