Objective To investigate the effect of combined anesthesia with etomidate and propofol on the elderly undergoing painless gastroscopy, and analyze its effects on systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR). Methods 100 elderly subjects with painless gastroscopy admitted to Deyang People’s Hospital from September 2021 to September 2022 were selected as the research objects, and were divided into the control group and the study group according to the random number table method, with 50 cases in each group. Research object in the control group were anesthetized with propofol alone, and research object in the study group were treated with etomidate on the basis of the control group. The anesthetic effects of the two groups were compared, and the changes of blood pressure, HR, oxygen saturation of blood (SaO2) and related cognitive function indexes were observed. Results The time of anesthesia induction, awakening and recovery of orientation in the study group were shorter than those in the control group (P<0.05). The mini-mental state examination（ MMSE） scores in the study group were higher than those in the control group 30 minutes after anesthesia (P<0.05). The levels of SBP and DBP of the study group were significantly higher than those of the control group 5 minutes after anesthesia (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P>0.05). Conclusion The combination of etomidate and propofol can be the first choice for elderly patients during painless gastroscopy. The anesthesia has quick effect, little impact on blood pressure, high safety, and relatively ideal recovery effect after anesthesia, which has clinical application value.