Background and aim: Delirium in surgical patients has a profound impact on postoperative outcomes. This study aimed to compare the effect of dexmedetomidine versus haloperidol in the incidence and severity of post-operative delirium in elderly patients undergoing elective orthopedic surgery under general anesthesia. Patients and methods: Sixty elderly patients scheduled for orthopedic surgery under general anesthesia were randomly allocated into three groups. In the control group, patients received normal saline. In the dexmedetomidine group, patients received dexmedetomidine 1 μg/kg over 20 minutes then continuous infusion at a rate of 0.2 to 0.7 μg/kg/h until end of surgery. In the haloperidol group, patients received haloperidol 2.5 mg IV bolus followed by continuous infusion of 0.5 to 2 mg/h until end of surgery. The primary outcome was the number of patients developed delirium and the degree of severity of postoperative delirium. The secondary outcomes were duration of surgery, hemodynamic variables and Visual analogue scale (VAS). Results: Hemodynamic variables (MAP and HR) were significantly lower in dexmedetomidine group when compared to haloperidol and control groups. VAS was significantly lower in dexmedetomidine group immediately postoperative and up to 4 hours. The incidence and the severity of postoperative delirium were significantly reduced in dexmedetomidine group Conclusion: The incidence and severity of post-operative delirium were significantly reduced with intraoperative administration of dexmedetomidine infusion when compared with haloperidol.