Objective To investigate the effect of different doses of dexmedetomidine on cognitive function in elderly patients after endoscopic retrograde cholangiopancreatography (ERCP). Methods A total of 120 elderly patients (≥65 years old) undergoing elective ERCP in the General Hospital of Northern Theater Command from May 2014 to January 2015 were recruited in this study. They were randomly divided into control group (group C), 0.5 μg(group D1) and 0.8 μg dexmedetomidine group (group D2), with 40 cases in each group. Dexmedetomidine of 1.0 μg/kg were infused before induction to the patients of the latter 2 groups as loading dose for 10 min, and then were given at 0.5 μg/(kg·h) (group D1) or 0.8 μg/(kg·h) (group D2) by continued infusion until the end of surgery. The group C was infused with the same volume of normal saline. The clinical data, such as general condition, intraoperative dosage of propofol, and incidences of adverse reactions were recorded. Venous blood samples were collected to detect the levels of tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6) and soluble protein 100-β (S-100β) by ELISA before operation (Ta), immediately after operation (Tb), and 24 h after operation (Tc). Mini-mental state examination (MMSE) was perfermed to test the occurrence of postoperative cognitive dysfunction (POCD) at 1 d before, 1 d and 3 d after operation. The data was analyzed by using SPSS statistics 19.0. Comparison among groups was performed by analysis of variance or Chi-square test. Results Compared with group C [(182.01±61.88)mg], the dosage of propofol was significantly lower in group D1 [(112.84±40.10)mg] and group D2 [(100.96±46.64)mg], both with significant difference (P<0.05). The plasma levels of TNF-α, IL-6 and S-100β were also obviously lower in group D1 and group D2 at Tb and Tc when compared with group C (all P<0.05). Statistical differences were seen in the incidences of body movement, hiccups and respiratory depression among the 3 groups (P<0.05). After operation there was 1 patient suffering from POCD in group D1, with the incidence rate of 2.5%, so was in group D2, and the rate was significantly lower than that of group C (8 cases, 20.0%, P=0.005). Conclusion Intraoperative infusion of dexmedetomidine can reduce the dosage of propofol and prevent adverse reactions in the elderly undergoing ERCP, and decrease the occurrence of POCD at the same time.