A 74-year-old man was admitted to the Emergency Room of our institution with worsening dysarthria, left-side weakness and hypoesthesia (NIHSS score: 5) since his awakening at 7:30 a.m. The evening before, he had gone to sleep at 10:30 p.m. Brain computed tomography (CT) and cervicocranial CT angiography showed low density attenuation of the right caudate nucleus head and lenticular nucleus and sub-total occlusion of ipsilateral middle cerebral artery (MCA) pre-bi/trifurcation Ml segment. Brain CT perfusion showed an ischemic core in the right striatal region, surrounded by a wide region of ischemic penumbra. Although the onset of symptoms, defined as “time last-seen well”, was 14 hours before presentation, the following worsening of neurological conditions (NIHSS score: 12) and the evidence of cerebral blood flow / cerebral blood volume mismatch at CT perfusion led us to propose neuroendovascular treatment on the basis of an off-label use. Neuroendovascular treatment by Penumbra system was achieved and the right MCA was only partially recanalized. The patient was discharged with NIHSS score of 12. At six months, modified Rankin scale score was 3. To the best of our knowledge, this is the first Italian case report describing a patient who underwent successful neuroendovascular treatment for a “wake-up stroke” without clinical worsening nor major complications and an acceptable clinical outcome. This was possible thanks to an extension of the therapeutic window guided by CT perfusion.