OBJECTIVES: Appropriate sedative and analgesic selection is essential to reduce patient discomfort and body movement to safely conduct endoscopic ultrasonography (EUS). However, few cases have examined sedation with propofol in EUS, and few studies the need for combined analgesia. In this study, we retrospectively evaluated the usefulness and safety of propofol without analgesics for sedation in biliopancreatic observational EUS. METHODS: This single-center retrospective study included 516 observational biliopancreatic EUS procedures using propofol alone performed between April 2021 and March 2023. The primary and secondary endpoints were the observational biliopancreatic EUS results obtained with propofol alone and adverse event occurrence, respectively. RESULTS: The median examination time and total propofol dose were 22 (range: 10-67) min and 186.5 (range: 50-501) mg, respectively. The median starting Richmond Agitation-Sedation Scale and Visual Analog Scale scores were -5 (range: -5-1) and 0 (range: 0-10), respectively. The median recovery time was 22 (range: 5-80) min. Adverse events occurred in 60 (11.6%) patients. Trainee-performed examination (odds ratio [OR] 3.52, 95% confidence interval [CI]: 1.63-7.60, CONCLUSIONS: During observational biliopancreatic EUS, propofol is useful as a single sedative and offers high patient satisfaction and relative safety.