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Background and Purpose: Unknown-onset strokes (UOS) have often been considered seperately from known-onset strokes (KOS), since emergency recanalization treatments are based on a time-window. Improvement in imaging-based selection and the advent of endovascular thrombectomy may lead us to reconsider this practice.Methods: We performed a retrospective, multicenter, cohort study of consecutive UOS treated by thrombectomy between December 2012 and December 2016. We compared UOS with proximal anterior circulation occlusion discovered beyond 6 hours from “last seen normal” with KOS for whom thrombectomy was started within 6 hours from onset. Time intervals from first found abnormal were recorded and compared with time intervals of KOS. Results were adjusted for age, initial National Institutes of Health Stroke Scale score, site of occlusion, diffusion weighted imaging Alberta Stroke Program Early CT Score, intravenous thrombolysis and use of general anesthesia.Results: Among 1246 strokes with anterior circulation occlusion treated by thrombectomy, 277 were UOS, with a “last time seen well” beyond 6 hours and DWI-FLAIR mismatch, and 865 were KOS who underwent groin puncture within 6 hours. Favorable outcome was achieved less often in UOS than KOS patients (45.2% vs. 53.9%, p=0.022). After pre-specified adjustment, this difference was not significant (adusted relative risk=0.91; 95%CI, 0.80 to 1.04; p=0.17). No differences in secondary outcomes were found except a marginal difference for excellent outcome (adjusted relative risk=0.83; 95%CI, 0.69 to 1.00; p=0.052), Time intervals from “first found abnormal” were significantly longer in UOS.Conclusion: Endovascular treatment of unknown-onset strokes with anterior circulation occlusion and DWI-FLAIR mismatch appears to be as safe and efficient as endovascular treatment of known-onset strokes within 6 hours from onset. This pattern of imaging could be used for patient selection when time of onset is unknown.