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Introduction: Extracranial vascular characteristics determine the accessibility of the large vessel intracranial occlusion for endovascular treatment (EVT) in acute ischemic stroke. We developed and validated a prediction model for failure of the transfemoral approach to aid clinical decision-making regarding EVT., Methods: A prediction model was developed from data of patients included in the Dutch multicenter MR CLEAN Registry (March 18, 2014, until June 15, 2016) with penalized logistic regression. Predictor variables were available prior to the EVT procedure and included age, hypertension, and extracranial vascular characteristics assessed on baseline CTA. The prediction model was internally validated, temporally validated within a second MR CLEAN Registry cohort (June 15, 2016, until November 1, 2017), and updated by re-estimating the coefficients using the combined cohort., Results: Failure of the transfemoral approach occurred in 7% of patients, in both cohorts (derivation cohort: n = 887, median age 71 years, interquartile range [IQR] 60-80, 52% men; validation cohort: n = 1,111, median age 73 years, IQR: 62-81, 51% men). The prediction model had a c-statistic of 0.81 (95% CI: 0.76-0.86) in the derivation cohort, 0.69 (95% CI: 0.62-0.75) at temporal validation, and 0.75 (95% CI: 0.71-0.79) in the final prediction model, with the following penalized β-coefficients for predictor age (per decade): 0.26, hypertension: -0.16, severe aortic arch elongation: 1.45, bovine aortic arch: 0.44, elongation of the supra-aortic arteries: 0.72, cervical ICA elongation: 0.44, and high-grade stenosis of the cervical ICA: 0.78., Conclusion: Our prediction model showed good performance for prediction of failure to reach the intracranial occlusion by the transfemoral approach., (© 2023 The Author(s). Published by S. Karger AG, Basel.)