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Purpose: The preponderance of evidence suggests that target vessel locations (TVL) are important predictors of outcomes in acute ischemic stroke (AIS). However, few studies have examined in detail their correlation in the natural history of a cohort of patients with ICA, M1 and M2 vessel occlusions who are eligible for, but untreated with, mechanical thrombectomy.Hypothesis: We hypothesize that, similar to the broader stroke cohort, there is a correlation between TVL and outcomes.Methods: The SOS and FIRST trials were prospective, multicenter studies evaluating the natural history of a stroke cohort eligible for mechanical thrombectomy but did not receive the treatment. Enrolled patients presented with symptoms of AIS due to LVO and were refractory or ineligible for rtPA treatment. Functional independence was defined as a mRS score 0-2 at 90 days. Incidence of death, intracranial hemorrhage (ICH), serious adverse events (SAEs), and mortality were assessed for association with TVL.Results: A total of 238 patients (median age: 71) met study criteria. Occlusions were reported in the ICA (32.5%), M1 (54.4%), M2 (8.9%), and basilar artery (1.7%). At 90 days, 9.2% of ICA, 12.1% of MCA M1, 25.0% of MCA M2, and 0.0% of basilar artery patients achieved functional independence as defined by a mRS score of 0-2. Although the rate of SAEs was similar between ICA (83.3%), M1 (81.4%), and basilar artery (75%), the rate was lowered in patients with M2 occlusion (61.9%, p<0.05). There were also significantly fewer mortalities associated with occlusion of the M1 (27.4%, p<0.01) and M2 (10.0%, p<0.01) when compared to ICA occlusions (40.8%).Conclusion: Similar to the broader patients with AIS, there is a significant correlation between TVL and outcomes in patients with LVO eligible for mechanical thrombectomy. Although occlusion of smaller vessels (i.e. M2) predicts better functional outcome, 75% of patients will not reach functional independence.