Abstract Background: Recently dexmedetomidine had been successfully used in conscious (moderate) sedation as a good competitive to popular agent (midazolam). Different concentrations of ketamine and propofol combinations (ketofol) were used for procedural sedation and analgesia. Objectives: The study was conducted to compare two techniques of moderate sedation for patients undergoing ERCP, using either dexmedetomidine or ketofol as regards hemodynamic, sedation, pain, respiratory effect, recovery time, patients’ and endoscopists’ satisfactions, and complications during and after the procedure. Patients and methods: Fifty patients were randomly allocated in one of two groups; dexmedetomidine group D (n= 25) received 1 lg/kg i.v. bolus over 10 min followed by 0.5 lg/kg/h or ketamine/ propofol (ketofol) group KP (n=25) received 1 mg/kg i.v. bolus followed by 50 lg/kg/min. The level of sedation was adjusted to achieve a Ramasy sedation scale (RSS) score of 4 in both groups of patients. Mean arterial pressure (MAP), heart rate (HR), peripheral oxygen saturation (SPO2), and facial pain score (FPS) were compared. Time to achieve RSS, modified Aldrete’s score (MAS) of 9–10 and the related complications were compared between groups. Patients’ and endoscopists’ satisfactions were compared. Total amount of rescue sedation was recorded.