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Background: Recent recommendations for mechanical thrombectomy (MT) of acute ischemic stroke (AIS) patients with emergent large-vessel occlusions (ELVO) appropriately award top tier evidence (TTE) to the same selective criteria that were employed in recent clinical trials. We sought to evaluate the safety and efficacy of MT in AIS patients with ELVO who fail TTE criteria in a prospective multi-center study.Methods: Data on consecutive AIS patients with ELVO who underwent mechanical thrombectomy were collected from 6 high-volume endovascular centers. Standard safety and efficacy outcomes were compared between patients meeting and failing TTE criteria.Results: TTE criteria for MT were fulfilled in 349 (60%) cases (mean age 63±18 years; 47% men; median admission NIHSS-score17 points, interquartile range 14-21), whereas 234 (40%) patients did not meet TTE criteria (mean age 62±19 years; 53% men; median admission NIHSS-score 16 points, interquartile range 9-21). (Table 1) The two most common reasons for failing TTE criteria were location of intracranial occlusion (n=144) and treatment window (n=108). In multivariate logistic regression models adjusting for potential confounders cases failing TTE criteria had similar safety (three-month mortality and symptomatic intracranial hemorrhage) and efficacy (three-month functional independence) outcomes with patients meeting TTE. Location of occlusion and proposed time-window according to TTE was also not related to any safety or efficacy outcome. (Table 2)Conclusions: Approximately 40% of AIS patients with ELVO offered MT do not fulfill TTE criteria for MT. Our multi-center experience indicates that MT may be offered to these patients with similar safety and efficacy to ELVO cases meeting TTE. Evidence-based medicine requires that health care providers understand published data and how those data might apply to a given patient’s treatment options. In a changing treatment environment this is a dynamic process.