Colonoscopy is an endoscopic procedure that examines the mucosa of the large intestine and distal terminal ileum for histopathological sampling and therapeutic procedures. Methods: Forty patients of both sexes candidates for colonoscopy were randomized to (D group & P group) each one included 20 patients: D Group: Dexmedetomidine was given as an initial loading dosage of 1 µg/kg i.v over ten minutes then received propofol 0.5mg/kg, then a continuous I.V. dexmedetomidine infusion (0.2–0.8) µg/kg/h was started until the procedure completed. P Group: The intravenous loading dose of propofol 2 mg/kg was given, then a continuous infusion of propofol 25–100 µg/kg/min was started until the procedure was completed. Results: The level of sedation was assessed using the Ramsay Sedation Score (RSS) showed a significant increase in the P group (2-2) compared to the D group activity (1-2) throughout 1-hour post-operatively. After 5 min of the procedure heart rate significantly decreased in group D then it became non-significant during the remaining time. The oxygen saturation % values showed a significant reduction in the P group (mean 95.45 ± 2.70) at 5 min of the procedure then it became non-significant during all remaining time. Although Bradycardia was more significantly higher in the D group, hypotension and respiratory complications were more significant higher in the P group. Also, the endoscopist was satisfied in the D group. Conclusion: In patients undergoing colonoscopy, dexmedetomidine combined with a low dose of propofol resulted in greater conscious sedation and adequate endoscopist satisfaction than propofol alone.