Background: Historically, hepatopancreatobiliary surgeons and gastroenterologists have undertaken endoscopic retrograde cholangiopancreatography (ERCP) using benzodiazepine sedation (BS). This is poorly tolerated by a substantial number of patients, which leads to its potential premature abandonment and subsequent additional investigations and therapeutics, and hence to the exposure of patients to avoidable risk and the health service to increased costs. Furthermore, concerns have been raised in the recent literature regarding safe sedation techniques. Objectives: The aim of this study was to compare the completion rates and safety profile of ERCP using BS vs. those of ERCP using light propofol anaesthesia (PA). Methods: We carried out a retrospective, case-matched comparison analysis of consecutive patients who underwent ERCP with BS vs. PA, in the presence of an anaesthetist, over a 2-year period. Benzodiazepine sedation consisted of midazolam, fentanyl and buscopan. Propofol anaesthesia consisted of propofol, fentanyl and buscopan administered via a mouth guard in a non-intubated patient. Patient demographics, complications and completion rates were recorded. Procedural monitoring included pulse oximetry, non-invasive blood pressure, electrocardiography and end-tidal CO2. Statistical analyses used t-tests to compare continuous variables and chi-squared and Fisher's exact tests to compare categorical variables. A P-value of < 0.05 was considered significant. Results: Of 252 patients included in the study, 128 (50.8%) received BS and 124 (49.2%) received PA. Median ages in the BS and PA groups were 69 years (range: 20-99 years) and 65 years (range: 26-98 years), respectively (P = 0.07). Median hospital stays in the BS and PA groups were 1 day (range: day case to 61 days) and 1 day (range: day case to 38 days), respectively (P = 0.61). Incidences of mild anaesthesia-related complications in the BS and PA groups were 2.3% and 2.4%, respectively (P = 0.97). There were no severe anaesthesia-related complications. Incidences of mild procedural complications in the BS and PA groups were 2.3% and 1.6%, respectively (P = 0.68). One severe procedural complication occurred in the PA group. Incidences of incomplete ERCP procedures in the BS and PA groups were 10.9% (n = 14) and 4.0% (n = 5), respectively (odds ratio = 2.92, 95% confidence interval 1.02-8.38; chi-squared test, P = 0.04; Fisher's exact test, P = 0.03). Conclusions: Propofol anaesthesia for ERCP carried out in the presence of an anaesthetist is safe and may improve procedural completion rates.