Objective: To compare the effect of oxycodone versus sufentanil combined with etomidate on painless gastroscopy in elderly patients. Methods: Sixty elderly patients underwent painless gastroscopy were included in this study in the First Center Hospital of Baoding from February 2017 to June 2017. Those patients of either sex, with American Society of Anesthesiologists physical status II, aged 65 to 77 years, weighing 46–63 kg, were divided into two groups (n=30): an oxycodone group (Group O) and a sufentanyl group (Group S). Patients were intravenously injected with oxycodone (0.05 mg/kg) in Group O and sufentanyl (0.05 μg/kg) in Group S. And then, all patients were intravenously injected with etomidate (0.2 mg/kg). When cough or movement occurred during gastroscopy, etomidate (0.05–0.1 mg/kg) was intravenously injected additionally. The MAP, HR, SpO2 and dosage of etomidate was recorded at the time points of before induction (T0), 2 minutes after induction (T1), 1 (T2) and 3 (T3) minutes after gastroscopy. The occurrence of cough, body movement, injection pain and respiratory depression, was recorded during the gastroscopy. And the waking time and the occurrence of adverse reactions, such as, dizziness, nausea and vomiting were recorded. Results: Compared with Group S, the waking time and dosage of etomidate decreased in Group O (P<0.05). Compared with Group S, the incidence of cough and body movement decreased in Group O (P<0.05). Compared with Group S, MAP and HR decreased in Group O (P<0.05). Compared with Group S, the incidence of nausea and vomiting decreased in Group O (P<0.05). For injection pain, dizziness and respiratory depression, there were no difference between the two groups (P>0.05). Conclusion: Efficacy oxycodone (0.05 mg/kg) combined with etomidate is superior to sufentanil for elderly patients with undergoing painless gastroscopy.