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Background: Endovascular therapy (EVT) effectiveness is established in ischemic strokes with large vessel occlusion (LVO) in the terminal ICA and M1, which was extended up to 24 hrs by recent DAWN trial results. However this benefit is not as well established in more distal (M2) occlusions, especially late presenters (beyond 6 hrs). We evaluated thrombectomy outcomes in M2 occlusions as compared to ICA/M1 across early and late time windows.Methods: In a prospective, multicenter, single arm, international registry (Trevo Retriever Registry), anterior circulation LVOs were stratified on clot location into M2 vs ICA/M1 and dichotimized into early vs late (0-6 vs 6-24 hrs). 90 day mRS (0-1 excellent, 0-2 good) were the primary outcomes; sICH and dissection were the secondary (safety) outcomes. Multivariate analyses identified pre-procedure variables independently correlating with good outcome in M2s.Results: 1581 patients were identified (1265 ICA/M1, 316 M2). The M2 and ICA/M1 groups were similar (age in both 68.4), IV-tPA (69.1 vs 69.7%, p=0.8) and same median/IQR ASPECTS 8 (7-9). M2 patients had lower NIHSS (13 vs 16, p<0.001). Higher good and excellent outcomes were observed in M2s (65.8% and 51.3%) compared to ICA/M1 (57.9% and 42.8%) (p=0.01). Similar outcomes were maintained beyond 6 hrs (64.8% good, 45.9% excellent in M2s vs 53.8% and 38.4% in ICA/M1) (p=0.08). Fig 1 shows the probabilities of good outcome in M2 vs ICA/M1 in relation to time, illustrating no association with time (p=0.4). Similar safety profiles were seen: sICH (0% M2 vs 0.7% ICA/M1, p=1.0) and dissections (0.3% M2 vs 0.4% ICA/M1, p=0.22). Age (aOR 0.96, 0.94-0.98 95% CI, p<0.001) and NIHSS (aOR 0.94, 0.9-0.98 95% CI, p<0.001) correlated with good outcome in M2, while IV-tPA did not have adjunctive benefit (aOR 0.72, 0.42-1.24 95% CI, p=0.24).Conclusion: Excellent and good outcomes may be achieved in distal LVO isolated to M2 similar to those with proximal occlusions. A benefit that can be reached up to 24 hrs.