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Background: The efficacy of endovascular therapy (EVT) in randomized clinical trials (RCTs) for acute strokes due to large vessel occlusion (LVO) led to AHA guidelines recommending EVT as standard of care for selected patients. However, many conditions were under-represented in the RCTs: ASPECTS <6, age ≥80 yo, NIHSS <6, onset to treatment >6 hrs and M2/ distal/ posterior circulation occlusions.Objective: We evaluated EVT outcomes in these populations compared to counterparts represented in the RCTs.Methods: A large multicenter international prospective cohort study of LVO patients treated with stent retriever thrombectomy (TREVO Registry) between 11/2013 and 4/2016 was analyzed. 90 day mRS was the primary outcome (0-2 good outcome). Multivariate logistic regression modeling was employed to evaluate EVT impact in the different groups.Results: Of 1000 patients, 81 had NIHSS <6 and 81.5% of those achieved a good outcome (aOR 3.6, 95% CI 1.9-6.8; p<0.001 compared with NIHSS ≥6) (Table 1). Over 80 yo, however, had low odds of independence (aOR 0.3, 95% CI 0.2-0.5; p<0.001 compared with <80 yo). Among 212 patients treated >6 hrs, 51% had a good outcome (aOR 0.78, 95% CI 0.55-1.1; p=0.17) compared to ≤6 hrs. Nearly half of patients with ASPECTS <6 (3-5) had a good outcome. Fig 1 illustrates mRS distributions stratified by the different subgroups. There were low rates of sICH for treated patients with NIHSS<6, age≥80, ASPECTS <6 or treatment >6 hrs. Fig 2 demonstrates the likelihood of good outcome by clot location. M2 and distal occlusions had the highest good outcome probabilities while proximal ICAs had the lowest (48.1%). More than half of vertebrobasilar patients achieved independence (54.8%).Conclusion: While effectiveness cannot be determined in the absence of medically treated controls, our analyses of real world data show several groups outside AHA guidelines may benefit from EVT. In particular, further study is needed to examine EVT benefits for mild stroke and M2 occlusions.