BACKGROUND AND OBJECTIVES: ERCP is a routinely carried out diagnostic and/or therapeutic procedure. It is a distressing procedure in awake patients. These patients require sedation mainly to minimize their anxiety and analgesics to alleviate pain and discomfort thereby enhancing patient's cooperation throughout the procedure 1 . Propofol has been traditionally used. Dexmedetomidine, a novel selective α2 agonist is known to produce sedation without compromising hemodynamic stability or causing respiratory depression. Objective of this study was to compare Propofol-Fentanyl combination with Dexmedetomidine-Fentanyl combination for providing satisfactory procedural sedation during ERCP. METHODS: 70 patients undergoing elective ERCP were divided into 2 groups of 35 each. Dexmedetomidine group patients received Fentanyl 1µg/kg and a loading dose of Dexmedetomidine1µg/kg over 10 minutes followed by a maintenance dose of 0.5 µg/kg/hr intravenously. Propofol Group patients received Fentanyl 1µg/kg and a loading dose of Propofol infused at 0.5mg/kg over 10 min followed by a maintenance dose of 2 mg/kg/hr intravenously. If patients showed signs of insufficient sedation as measured by Richmond Agitation Sedation Scale (RASS) they were supplemented with rescue Propofol bolus doses of 0.5 mg/kg. Sedation score and vitals were assessed every 5 minutes till the end of the procedure and every 5 minutes for 15 minutes during recovery. RESULTS: At the end of 15 minutes (pre-procedure), RASS in Dexmedetomidine group was -2.89±0.71 and RASS in the Propofol group was -3.31±0.53. Propofol group achieved the desired targeted RASS of more than -3 at 15 minutes. 22% of patients in Dexmedetomidine group and 2.8% of the patients in the Propofol group did not achieve RASS of -3 even after 15 minutes of infusion. Mean RASS over entire ERCP in Dexmedetomidine group was -3.18±.41 and in the Propofol group was -3.31±.39. Mean RASS over entire ERCP in Dexmedetomidine group was lesser than Propofol but there was no statistically significant difference (p=0.134) CONCLUSION: The combination of Propofol with Fentanyl achieved better overall conditions for ERCP compared to the combination of Dexmedetomidine with Fentanyl.