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Objective: We aimed to assess the hospital frailty risk score on the inpatient mortality, morbidity, and health care resource utilization among endoscopic retrograde cholangiopancreatography (ERCP)-related hospitalizations., Background: Data regarding the inpatient mortality, morbidity, and health care resource utilization of ERCP among frail individuals remain limited., Materials and Methods: Using the Nationwide Inpatient Sample, we compared the odds of inpatient mortality and morbidity of ERCP-related hospitalizations among individuals with low frailty scores, intermediate frailty scores (IFSs), and high frailty scores (HFSs)., Results: Overall, 776,025 ERCP-related hospitalizations were recorded from 2016 to 2020. 552,045 had a low frailty score, whereas 217,875 had an IFS, and 6105 had an HFS. Frail individuals had a 5-fold increase in mortality [IFS: adjusted odds ratio (aOR) = 4.81, 95% CI: 3.77-6.14; HFS: aOR = 4.62, 95% CI: 2.48-8.63]. An IFS was associated with a 24% increase in post-ERCP pancreatitis (aOR = 1.25, 95% CI: 1.11-1.41), a 3-fold increase in post-ERCP bleeding (aOR = 2.59, 95% CI: 1.82-3.67), and a 2-fold increase in post-ERCP duct perforation (aOR = 1.91, 95% CI: 1.38-2.64). Frail individuals experienced higher odds of in-hospital morbidity, including secondary sepsis, respiratory failure, acute kidney injury, cerebrovascular accidents, deep vein thrombosis, and pulmonary embolism., Conclusions: In summary, our study presents strong evidence in support of using the hospital frailty risk score as an index to predict mortality and morbidity during ERCP-related hospitalizations. Additional caution is warranted in the management of frail individuals undergoing ERCP., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)