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Background and Purpose: Preclinical stroke scales may help identify patients likely to have large vessel occlusion (LVO) to facilitate rapid triage to thrombectomy-capable stroke centers. Scale misclassification may result in inaccurate decisions and possible harm. Pre-existing leukoaraiosis has been shown to attenuate the association between deficit type and stroke severity. We sought to determine whether leukoaraiosis affects the predictive ability of 5 commonly used LVO scales.Materials and Methods: We retrospectively analyzed 274 consecutive stroke patients with available brain MRI and vessel imaging. The following LVO scales were used: 3 Item Stroke Scale (3I/SS), Field Assessment Stroke Triage for Emergency Destination (FAST-ED), Rapid Arterial Occlusion Evaluation (RACE), Vision, Aphasia, Neglect (VAN) score, and Cincinnati Prehospital Stroke Severity Scale (CPSSS). For diagnostic scale accuracy, we assessed sensitivity, specificity, positive predictive value, negative predictive value, and kappa. Multivariable logistic regression was used to determine the scales’ predictive ability after adjustment for leukoaraiosis and potential confounders.Results: In unadjusted analyses, all scales predicted LVO (n=46; P<0.01, each), though leukoaraiosis attenuated diagnostic accuracy and was associated with more false negative diagnoses. After adjustment, the FAST-ED (OR 3.2 [1.1-9.5]; P=0.033), and RACE (OR 3.7 [1.3-10.8]; P=0.015) but not 3I/SS (OR 5.4 [0.86-33.9]); P=0.073), VAN (OR 2.5 [0.8-7.2]), and CPSSS (OR 2.8 [1.0-8.0]) predicted LVO.Conclusion: The diagnostic accuracy of the tested LVO scales was attenuated by moderate-tosevere leukoaraiosis. If confirmed, this information may aid acute decision making and the design of studies that require LVO scale screening of patients likely to have concomitant leukoaraiosis.