Background and AimsEndoscopic transpapillary gallbladder drainage (ETGBD) is a therapeutic option for gallstone-related gallbladder disease in non-surgical candidates. However, the optimal stenting strategy and follow-up has not been established. We aimed to determine whether there was a decreased need for unplanned reintervention in patients undergoing placement of two transpapillary gallbladder stents as compared to one. MethodsWe performed a multicenter retrospective analysis of patients undergoing ETGBD between June 2013 and October 2022. The primary outcome was clinical success as defined by resolution of symptoms without the need for another drainage strategy. Secondary outcomes included the adverse events of post-ERCP pancreatitis, cholangitis, bleeding, perforation, or death. Factors associated with placement of two stents, unplanned reintervention, and adverse events were assessed. ResultsWe included 75 patients undergoing ETGBD, with a median follow-up of 407 days (IQR: 71-1504). Technical and clinical success were 88.2% and 81.3%, respectively. Unplanned reintervention was significantly lower in the double stenting group (0% vs. 25.4%, P=0.02). Use of a 7 French stent (OR: 15.5; 95% CI: 1.9-125; p=0.01) and presence of a percutaneous cholecystostomy tube (OR: 10.8; 95% CI: 2.8-41.3; p=0.001) were associated with placement of two stents. There was no significant difference in adverse events between groups (OR: 0.9; 95% CI: 0.09-8.8; P=0.94). ConclusionsETGBD is safe and effective in non-operative candidates. Single transpapillary gallbladder stenting is associated with more unplanned reinterventions, and 7 French stent diameter and prior percutaneous cholecystostomy tube may be associated with ability to place a second stent. Endoscopists should consider planned exchange of solitary transpapillary gallbladder stents or interval placement of a second stent if placement of two stents was unsuccessful at the index procedure.