Objective To explore the clinical effects of small dose of ketamine combined with propofol on stress response in elderly patients undergoing endoscopic retrograde cholangiopancreatography(ERCP). Methods Thirty-eight ASA gradeⅠ-Ⅲ elderly patients in need of ERCP were randomly divided into two groups: small dose of ketamine combined with propofol infusion anesthesia group (KP group, n=19) and propofol infusion group (P group, n=19). The recovery time, orientation time, body movement during operation, heart rate(HR), mean artery pressure(MAP), pulse oxygen saturation(SpO2), side-effects, and the levels of plasma cortisone(Cor) and glucose(Glu) were compared between the two groups and different time points, including before and after anesthesiological induction, before and after endoscopy, and after operation. Results After anesthesiological induction, MAP was significantly decreased in both P group[(98.2±18.7) vs (81.6±13.3) mmHg, P＜0.05] and KP group[(95.7±16.3) vs (85.8±14.8)mmHg, P＜0.05]. MAP and HR after anesthesiological induction, before and after endoscopy were significantly different between P group and KP group[MAP:(81.6±13.3) vs (85.8±14.8)mmHg, (81.8±12.2) vs (84.2±15.9)mmHg, (97.7±18.6) vs (92.5±16.1)mmHg, P＜0.05; HR:(14.5±2.1) vs (16.6±2.5)beats/min, (14.9±1.1) vs (16.2±3.1)beats/min, (19.9±4.1) vs (17.1±1.2)beats/min, P＜0.05]. Mean operation time was significantly shorter in KP group than in P group[（111±18.6）vs（123±26.4）min; P＜0.05]. The side effects incidence was significantly lower in KP group than in P group(21.1% vs 52.6%, P＜0.05). There was no significant difference in the recovery time and SpO2 between the two groups. The levels of plasma Cor and Glu during operation were significantly higher in P group than in KPgroup(P＜0.05). Conclusion Small dose of ketamine combined with propofol can maintain hemodynamic stability in ERCP and decrease perioperative stress response. It is safe and available for anesthesia in elderly patients undergoing ERCP.