Objective To investigate clinical application and safety evaluation of sedative demulcent anesthesia in therapeutic endoscopic retrograde cholangiopancreatography (ERCP).Methods Totally 1660 patients underwent ERCP at the First Hospital of Lanzhou University were prospectively divided into two groups: venous sedative demulcent group (n=800, using sufentanil and midazolam and propofol continuing infusion) and conventional sedative demulcent group (n=860, using common medicine). The heart rate (HR), respiration (R), blood pressure (BP) and peripheral oxygen saturation (SpO2) of pre-anesthesia, post-anesthesia, during operation and after analepsia in every group were detected. The narcotism was evaluated by Ramsaymin grading method and the related adverse reactions such as cough, restlessness, harmful memory, and abdominal pain after operation were recorded. Results Compared with conventional sedative demulcent group, vital signs of patients in venous sedative demulcent group were more stable. For postoperative adverse reactions, abdominal pain, abdominal distension and nausea and vomiting were respectively 4.4%(35/800), 2.6%(21/800) and 3.6%(29/800) in venous sedative demulcent group, which were respectively higher of the incidence of 36.3%(312/860), 49.0%(421/860) and 53.0%(456/860) in conventional sedative demulcent group (P＜0.01). The postoperative satisfaction and adverse reactions recall between venous sedative demulcent group and conventional sedative demulcent group was respectively significant different (96.9% vs. 2.9%, 4.8% vs. 97.9%, P＜0.01). Conclusion Sufentanil and midazolam and propofol continuing infusion have good effect of sedative demulcent anesthesia, which can be widely used.