BACKGROUND Colonoscopy is an uncomfortable and short procedure needing brief sedation with fast emergence. METHODS This research is going to measure intravenous dexmedetomidine against propofol-fentanyl combination in terms of sedation-analgesia and hemodynamic changes in non-obligatory colonoscopy procedures. 70 colonoscopy candidates aged between 20 to 70 years were enrolled in this study while separated into two random equal-sized groups (p stands for propofol- & D stands for dexmedetomidine groups). All patients were premedicated with 0.03 mg/kg midazolam and 1 µ/kg fentanyl, 10 minutes and 5 minutes before the colonoscopy process, respectively. 0.5-1 mg/kg propofol for the P group and 1 µ/kg dexmedetomidine for the D group were infused in one minute before the initiation of the procedure following by normal saline as maintenance liquid and boluses of 25-50 µg fentanyl as needed. RESULTS These variables were entered into a datasheet: hemodynamic changes, sedation-analgesia level throughout the procedure, and patients’ and physicians’ contentment. The mean arterial pressure changes were similar and insignificant in the two groups (82.44±12.34 vs. 87.63±22.45 p=0.2). The D group had lower heart rates in comparison with the P group (72.51±16.7 vs. 81.56±15.71 p=0.001). The P group was deeply to moderately sedated and required a significantly lower doses of fentanyl rescue treatment (71.02±25.63 vs. 91.45±38.62 µg p=0.003). The P group was associated with a high incidence of apnea and was significantly superior to the D group in the matter of satisfaction (43% against 77%). CONCLUSION Colonoscopists’ contentment rates were identical in both groups. Propofol infusion is more satisfactory yet having more respiratory depression possibility in comparison with dexmedetomidine infusion in colonoscopy candidates.