What Is Known and Objective. Appropriate doses of sedatives are crucial for a successful, painless upper gastrointestinal endoscopy. Hence, we conducted a randomized controlled study to explore the effects of dezocine on the median effective dose (ED50) of the etomidate-propofol (E-P) mixture in prohibiting response to gastroscope insertion in patients of different genders. Methods. Patients aged 18–65 years enrolled in the study of the American Society of Anesthesiologists (ASA) with physical status I or II undergoing elective gastroscopy were included. Patients were randomly assigned to the male normal saline group (MS group), male dezocine group (MD group), female normal saline group (FS group), and female dezocine group (FD group). All patients were anesthetized with an E-P mixture of 1 : 1. The FD and MD groups were intravenously injected (i.v.) 50 µg/kg dezocine 5 min before anesthesia, while the FS and MS groups were injected with an equal volume of normal saline 5 min before anesthesia. According to the preexperiment, the initial dose of the E-P mixture for the FD and MD groups was 0.4 and 0.3 mL/kg for the FS and MS groups. The variation proportion was set as 0.9 between dosages. Dixon’s up-and-down method was adopted to confirm the dose of the E-P mixture for the next patient, which was reduced if the insertion was performed successfully; otherwise, the dose was increased. Centered isotonic regression was employed to determine the ED50 and 90% confidence interval (CI) values of the E-P mixture in the four groups. The total amount of E-P mixture consumed was recorded as well as the adverse events of patients. Results. The ED50 and 90% CI of the MS, MD, FS, and FD groups were 0.315 (0.285–0.349), 0.206 (0.175–0.237), 0.329 (0.305–0.355), and 0.207 (0.188–0.227) mL/kg, respectively. The MD group was <MS group ( P ≤ 0.001 ), and the FD group was <FS group ( P ≤ 0.001 ); no statistical difference was observed between the MS and FS groups and MD and FD groups. Dezocine reduced the total amount of E-P mixture consumed and the overall incidence of adverse events. What Is New and Conclusion. Dezocine significantly decreased the ED50 of the E-P mixture in inhibiting the response of patients to gastroscope insertion and the occurrence rate of adverse events. Further, gender had no impact on the ED50 of the E-P mixture.