Objective To assess the influence of age on the safety of propofol mono-sedation for adult patients undergoing painless gastroscopy. Methods A retrospective study was conducted on data of 321 patients scheduled for painless gastroscopy with propofol mono-sedation. According to the age, patients were divided into youth group (116 cases, 18-44 years), middle-aged group (103 cases, 45-59 years) and elderly group (102 cases, 60-80 years). The procedure time, the total dosage of propofol, the occurrence of airway obstruction or hypoxemia, the use of airway interventions including airway opening maneuvers and facemask ventilation, lowest SpO2, adverse cardiovascular events (including hypertension, hypotension, tachycardia, and bradycardia), and the use of ephedrine during painless gastroscopy were observed. Results There was significant difference regarding the total dosage of propofol among youth group (173.2±47.0 mg), middle-aged group (158.8±41.3 mg) and elderly group (137.8±26.3 mg) (F=21.761, P<0.001). The total dosage of propofol was significantly lower in the elderly group compared with the middle-aged group (P<0.017) and youth group (P<0.017), and that in the middle-aged group was significantly lower than that in the youth group (P<0.017). The incidence of hypoxemia was 12.9％ (15／116) in the youth group, 15.5％ (16／103) in the middle-aged group and 25.5％ (26／102) in the elderly group, with significant difference among three groups (χ2=5.711, P=0.017). Moreover, the incidence of hypoxemia was significantly higher in the elderly group compared with the middle-aged group (P<0.017) and youth group (P<0.017). The incidences of hypotension, bradycardia and total adverse cardiovascular events were 5.2％ (6／116), 4.9％ (5／103) and 11.8％ (12／102), 1.7％ (2／116), 2.9％ (3／103) and 7.8％ (8／102), and 11.2％ (13／116), 10.7％ (11／103) and 20.6％ (21／102) respectively in youth, the middle-aged and the elderly group. There were no significant differences in the above indicators among the three groups (P>0.05). However, compared with those of the young and the middle-aged patients, the occurrence of hypotension, bradycardia and total adverse cardiovascular events in the elderly patients were on the rise. There were no significant differences among the three groups in other indices(P>0.05). Conclusion Total dosage of propofol may need to be decreased gradually with the increase of age of patients undergoing gastroscopy with propofol mono-sedation. Compared with young and middle-aged patients, elderly patients have a significantly higher incidence of hypoxemia, with a tendancy of total adverse cardiovascular events increase, so the safety of painless gastroscopy is reduced for these patients.