Objective To study the effect of anesthesia with a dexmedetomidine-sufentanil combination in patients undergoing endoscopic retrograde cholangiopancreatography(ERCP), we observe the hemodynamic variation and the incidence of adverse reactions. Methods Fifty-two patients with ERCP were randomized and divided into two groups each 26 cases: study group using anesthesia with a dexmedetomidine-sufentanil combination and control group using local anesthetics with lidocaine aerosol. Clinical results were compared. Characteristic and demography in two groups were evalua-ted. Mean arterial pressure, heart rate and pulse oxygen saturation value were recorded with examination of a total 11 times including before anesthesia, and 5 min, 10 min after intravenous anesthetics, and at the time of entering the endoscopy, and the time of 1 min, 3 min, 5 min, 10 min, 15 min during ERCP, and at the end of ERCP endoscopic operation. The adverse effect during ERCP was observed including cough, nausea and vomiting, dysphoria, restlessness and respiratory depression. The degree of comfort and acceptance of patients were recorded on the first day after ERCP. Results Hemodynamic variation and the incidence of adverse reactions were significantly lower in study group than those in control group respectively(P<0.05). There was no significant difference in pulse oxygen saturation between two groups. The accep-tability to receive ERCP was 100% in study group and 65% only in control group. The operative time was significantly shorter in study group than that in control group(P<0.05). Conclusions Anesthesia with dexmedetomidine-sufentanil combination under monitored care for ERCP could have an advantage of more safe and more comfort on patients and acceptance.