Background:The aim of this clinical study was to evaluate the efficacy of neurobehavioral, hemodynamics and sedative characteristics of dexmedetomidine compared with morphine and midazolam-based regimen after cardiac surgery at equivalent levels of sedation and analgesia in improving clinically relevant outcomes such as delirium.Methods:Sixty patients were randomly allocated into one of two equal groups: group A = 30 patients received dexmedetomidine infusion (0.4–0.7 μg/kg/h) and Group B = 30 patients received morphine in a dose of 10–50 μg/kg/h as an analgesic with midazolam in a dose of 0.05 mg/kg up to 0.2 mg/kg as a sedative repeated as needed. Titration of the study medication infusions was conducted to maintain light sedation (Richmond agitation-sedation scale) (−2 to +1). Primary outcome was the prevalence of delirium measured daily through confusion assessment method for intensive care.Results:Group A was associated with shorter length of mechanical ventilation, significant shorter duration of intensive care unit (ICU) stay (P = 0.038), and lower risk of delirium following cardiac surgery compared to Group B. Group A showed statistically significant decrease in heart rate values 4 h after ICU admission (P = 0.015) without significant bradycardia. Group A had lower fentanyl consumption following cardiac surgery compared to Group B.Conclusion:Dexmedetomidine significantly reduced the length of stay in ICU in adult cardiac surgery with no significant reduction in the incidence of postoperative delirium compared to morphine and midazolam.