Background/Objectives: We assessed the impact of frailty on outcomes of endoscopic retrograde cholangiopancreatography (ERCP) in the United States. Methods: The National Readmission Database (2016–2020) was used to identify index and 30-day ERCP readmissions, which were categorized into low-frailty, intermediate-frailty, and high-frailty groups based on the Hospital Frailty Risk Score (HFRS). Outcomes were then compared. Results: Of 885,416 index admissions, 9.9% were readmitted within 30 days of ERCP. The odds of 30-day readmission were higher in the intermediate-frailty group (12.59% vs. 8.2%, odds ratio [OR] 1.67, 95% confidence interval [CI] 1.64–1.71, p < 0.001) and the high-frailty group (10.57% vs. 8.2%, OR 1.62, 95% CI 1.52–1.73, p < 0.001) compared to the low-frailty group. On readmission, a higher HFRS also increased mean length of stay (intermediate-frailty vs. low-frailty: 8.49 vs. 4.22 days, mean difference (MD) 4.26, 95% CI 4.19–4.34, p < 0.001; high-frailty vs. low-frailty: 10.9 vs. 4.22 days, MD 10.9 days, 95% CI 10.52–11.28, p < 0.001) and mean total hospitalization charges (intermediate-frailty vs. low-frailty: $118,996 vs. $68,034, MD $50,962, 95% CI 48, 854–53,069, p < 0.001; high-frailty vs. low-frailty: $195,584 vs. $68,034, MD $127,550, 95% CI 120,581–134,519, p < 0.001). The odds of inpatient mortality were also higher for the intermediate-frailty and high-frailty compared to the low-frailty subgroup. Conclusions: Frailty was associated with worse clinical outcomes after ERCP.