Recent studies suggest that sedation provided by anaesthesia professionals may be less protective against serious adverse events than previously believed, however, data are lacking regarding endoscopic retrograde cholangiopancreatography (ERCP). Using the clinical outcomes research initiative national endoscopic database (CORI-NED), we aimed to assess whether mode of sedation was associated with rates of unplanned interventions (UIs) during ERCP.All subjects from CORI-NED undergoing ERCP from 2004 to 2014 were identified and stratified into three groups based on the initial mode of anaesthesia: endoscopist-directed sedation (EDS), monitored anaesthesia care without an endotracheal tube (MAC-WET) and general endotracheal anaesthesia (GEA). The primary outcome was UIs. To assess the impact of sedation mode on UIs, multivariable logistic regression models were created adjusting for demographic, physician and procedure-level variables.Population-based study.26698 ERCPs were analysed (7588 EDS, 8395 MAC-WET, 10715 GEA). UIs occurred in 320 ERCPs (1.2%). EDS was associated with a higher risk of UIs compared with sedation administered by an anaesthesia professional (OR 1.86, 95%CI 1.44 to 2.42). Additional factors associated with a higher risk of UIs included ASA class IV compared with class II (OR 3.18, 95%CI 2.00 to 5.06) and ERCPs done in community (OR 1.41, 1.04 to 1.91) and health maintenance organisations (OR 3.75, 2.01 to 6.99) hospitals.EDS is associated with a higher risk of UIs during ERCP compared with sedation administered by an anaesthesia professional. Higher ASA class and procedures performed in non-university hospitals were also associated with a higher risk of UIs. This study suggests that, when available, sedation using an anaesthesia professional should be utilised for ERCP.