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The authors evaluated 1073 patients with anterior circulation stroke undergoing mechanical thrombectomy between 2010 and 2016. Patients with wake-up stroke and daytime-unwitnessed stroke were compared with controls receiving mechanical thrombectomy as the standard of care. There was no significant difference in good functional outcome between patients with wake-up stroke and controls. Outcome in patients with daytime-unwitnessed stroke was inferior compared with controls. Groups did not differ in all-cause mortality at day 90 and the rate of symptomatic intracranial hemorrhage. They conclude that mechanical thrombectomy in selected patients with wake-up stroke allows a good functional outcome comparable with that of controls.