Background: This study was conducted to compare the efficacy and effects of dexmedetomidine and midazolam in preoperative sedation., Materials and Methods: A total of 125 patients in American Society of Anaesthesiologists (ASA) I-II were divided into three groups: Group I (n = 40) for controls, Group II (n = 40) for Dexmedetomidine (1 μg/kg), and group III was the midazolam group (n = 45). Group III was further divided into three subgroups according to the doses of midazolam: Group IIIA (n = 15) received 0.02 mg/kg, group IIIB (n = 15) received 0.04 mg/kg, and group IIIC (n = 15) received 0.06 mg/kg of midazolam. Drugs were infused over a 10-minute period with appropriate monitoring. Ramsay and visual analog scores, for sedation and anxiety, respectively, and mean arterial pressure, heart rate, and SpO(2) measurement, including respiratory rates were recorded, every 5 minutes for 30 minutes following infusion., Results: There was marked sedation and a decrease in anxiety in groups II and IIIC (P < 0.01). Mean arterial pressure (MAP) and heart rate (HR) decreased significantly in group II (P < 0.01 and P < 0.05, respectively), but there was no associated hypotension (MAP <60 mm Hg) or bradycardia (HR <50 bpm) (P < 0.05). Respiratory rates and SpO(2) values decreased in groups II, IIIA, IIIB, and IIIC. The differences in respiratory rates were not significant (P > 0.05); however, decrease in SpO(2) was significant in group IIIC (P < 0.01)., Conclusions: Dexmedetomidine was as effective as higher doses of midazolam in sedation. The hemodynamic and respiratory effects were minimal. Although dexmedetomidine caused significant decrease in the blood pressure and heart rate, it probably just normalized increased levels caused by preoperative stress.