BACKGROUND: Studies have reported that certain adverse reactions can occur during painless gastroscopy examination. Knowing how to decrease the risks and incidence of adverse reactions is of great importance. OBJECTIVE: To investigate whether topical pharyngeal anesthesia combined with intravenous anesthesia is superior to intravenous anesthesia alone in patients undergoing painless gastroscopy and to determine whether this combined approach had any additional benefits. METHODS: Three hundred patients undergoing painless gastroscopy were randomly assigned to either the control group or the experimental group. In the control group, patients were anesthetized with propofol, while patients in the experimental group received propofol combined with 2% lidocaine spray for topical pharyngeal anesthesia. Hemodynamic parameters before and after the procedure, including the heart rate (HR), mean arterial pressure (MAP), and pulse oxygen saturation (SPO2) were recorded. Any adverse reactions experienced by the patient, including choking and respiratory depression, and the total dosage of propofol required during each procedure were also documented. RESULTS: Compared with pre-anesthetic data, the HR, MAP, and SPO2 were reduced after the completion of the painless gastroscopy procedure in both groups. However, the HR, MAP, and SPO2 measurements taken after the gastroscopy were significantly lower in the control group than those of the experimental group (P< 0.05); thus, the hemodynamic parameters of the experimental group were more stable. Compared with the control group, there was significant reduction in the total amount of propofol administered in the experimental group (P< 0.05). The incidence of adverse reactions, including choking and respiratory depression, was significantly lower in the experimental group (P< 0.05). CONCLUSION: The results demonstrated that the application of topical pharyngeal anesthesia in painless gastroscopy can significantly reduce the incidence of adverse reactions. Thus, the combination of topical pharyngeal and intravenous anesthesia is worthy of clinical application and promotion.