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Introduction Frailty is common among patients with acute ischemic stroke (AIS), yet its influence on management, hospital resources, and outcomes remains undefined. Our objective was to investigate the association between frailty and access to AIS interventions, in-hospital mortality, discharge disposition, and resource utilization.Materials and Methods The National Inpatient Sample was queried for adults with a primary diagnosis of AIS from January 2016 to December 2021. Frailty risk was categorized based on the Hospital Frailty Risk Score (HFRS) as low (score <5), intermediate (5-15), or high (>15). Differences across frailty groups were assessed using chi-square tests for categorical variables and ANOVA or Kruskal-Wallis tests for continuous variables. Outcomes included rates of acute interventions (intravenous thrombolysis [IVT] or mechanical thrombectomy [MT]), in-hospital mortality, discharge disposition (routine vs. non-routine), length of stay (LOS), and total charges. Multivariable regression models were employed to adjust for age, sex, race/ethnicity, comorbidities (e.g., atrial fibrillation, diabetes), NIH Stroke Scale scores, and acute interventions (IVT and MT, where appropriate).Results Among 1,753,224 AIS admissions, frailty risk was low in 20.7%, intermediate in 58.6%, and high in 20.8%. Compared with patients at high-frailty risk, those at low and intermediate risk had significantly lower odds of in-hospital mortality (adjusted odds ratio [aOR] 0.06 and 0.36, respectively; p < 0.01) and higher odds of routine discharge (aOR 2.71 and 1.63; p < 0.01). LOS and total charges increased stepwise across frailty categories from lowest to highest risk group (p < 0.01). High-frailty patients were also more likely to receive IVT and MT (p<0.01) and had a shorter time to MT but longer time to IVT (p < 0.01).Conclusion Frailty risk represents an independent predictor of higher in-hospital mortality, non-routine discharge, and greater resource use in patients with AIS. Although high-frailty patients were more likely to receive IVT/MT and underwent earlier MT, they experienced delayed IVT. The incorporation of frailty assessment in patients with AIS could aid risk stratification and optimize treatment decisions, potentially improving outcomes in this high-risk population.Disclosures R. Tatit: None. J. Rios-Zermeno: None. S. English: None. C. Baccin: None. J. Meschia: None. R. Tawk: None.