Objective: To observe the anesthetic effect of different doses of dexmedetomidine combined with propofol in endoscopic retrograde cholangiopancreatography (ERCP), and to explore the appropriate dose of dexmedetomidine combined with propofol. Methods: 160 patients with ERCP under intravenous anesthesia were randomly divided into four groups. Group D1, group D2 and group D3 were infused with Dex loading of 1.0 μ g · kg^-1 within 10 minutes, then maintained anesthesia with 0.3, 0.5 and 0.7 μ g · (kg · h) ^{- 1}Dex combined with propofol, and group C was given the same amount of normal saline. Heart rate, mean arterial pressure, hemodynamic parameters, respiratory rate, percutaneous oxygen saturation, and serum cortisol concentration were recorded before anesthesia (T0), at the time of unconsciousness (T1) and at the time of duodenoscope entering esophagus (T2), propofol dosage, operation time, recovery time, adverse reactions, etc. Results: Compared with group C, MAP and HR of experimental group at T1 and T2 and RR at T2 were significantly decreased (P<0.05); MAP and HR in group C and group D1 were significantly increased (P<0.05), while those in group D3 were decreased (P<0.05), but the change range of group D2 was small, and the difference was not statistically significant (P>0.05). There was no significant difference in SpO2 among the four groups at each time point (P>0.05). The dosage of propofol, serum cor concentration at T2 and 10 min after operation in the experimental group were significantly decreased (P<0.05), and the recovery time in D3 group was longer than that in the other three groups, with statistical significance (P<0.05), but they were all within the clinical acceptable range. The incidence of adverse reactions of body movement, nausea and vomiting and respiratory depression was high in group C and D1. Bradycardia occurred in 4 cases in group D3. Atropine treatment may be related to the dose and speed of DEX administration. The incidence of adverse reactions in group D2 was the lowest (P<0.05). Conclusion: Dex combined with propofol for ERCP anesthesia can reduce the dosage of propofol, maintain the stability of hemodynamics and respiratory parameters, reduce the stress reaction and the incidence of adverse reactions, which can be safely used in clinical practice. The recommended dose of Dex is 0.5 μ g · (kg · h) ^{- 1}.