Objectives: Cardioembolic stroke has a poor prognosis. We evaluated the region-dependent efficacy of endovascular therapy (EVT) based on diffusion-weighted imaging-Alberta Stroke Program Early CT Score (DWI-ASPECTS)., Methods: This post-hoc analysis of the RELAXED study, which investigated the optimal timing of rivaroxaban to prevent nonvalvular atrial fibrillation (NVAF) recurrence in patients with acute ischemic stroke (AIS), included NVAF patients admitted with AIS or transient ischemic attack in the middle cerebral artery (MCA), with internal carotid artery (ICA), M1, or M2-MCA occlusion. Relationships between DWI-ASPECTS region and functional outcome (modified Rankin Scale [mRS]), mortality, recurrence, and hemorrhagic stroke were compared between patients with and without EVT, and adjusted odds ratios for age, pre-stroke mRS, National Institutes of Health Stroke Scale (NIHSS), ICA occlusion, infarct size, recombinant tissue plasminogen activator (rt-PA) use, and onset-to-hospitalization time were estimated., Results: EVT patients had significantly lower hemoglobin levels, higher median NIHSS scores, more lentiform nucleus infarcts, ICA or M1-MCA occlusions, treatment with rt-PA, and fewer M3, M5, or M6 infarcts and M2-MCA occlusions than no-EVT patients. EVT patients had shorter onset-to-hospitalization times and more frequent favorable functional outcomes (p=0.007). Mortality, recurrent ischemic stroke, and hemorrhagic infarction were similar in both groups. EVT was associated with significantly better functional outcomes among patients with insular ribbon (p=0.043) and M3 (p=0.0008) infarcts. M3 patients had significantly fewer rt-PA and EVT, and longer onset-to-hospitalization times., Conclusions: An occlusion in the insular ribbon or M3 region was associated with favorable functional outcomes in patients treated with EVT after cardioembolic stroke., Competing Interests: Declaration of Competing Interest K.U. received lecture fees from Daiichi-Sankyo. M.Y. received lecture fees from Boehringer Ingelheim, Bayer, Daiichi-Sankyo, Pfizer, BMS, Takeda, Sumitomo Dainippon, Sanofi, Otsuka, CSL Behring, Eisai, Tanabe-Mitsubishi, Medtronic, Boston Scientific, and Sekisui Medical and research support from Sanofi, Boehringer Ingelheim, and Daiichi-Sankyo. K.T. received lecture fees from Nippon Boehringer Ingelheim, Bayer Yakuhin, Daiichi-Sankyo, and BMS. E.M. received lecture fees from Johnson & Johnson, Otsuka, Novartis, Daiichi-Sankyo, Sumitomo Dainippon Pharma, Sosei, Kyowahakko-Kirin, Toshiba, Medtronic, and Nihon Medi-Physics and research support from Eisai, Daiichi-Sankyo, Novartis, Fuji Film RI, General Electric, MHWL, MEXT, and JSPS. T. Hirano received lecture fees from Astellas, Bayer, Boehringer Ingelheim, BMS, CSL Behring, Daiichi-Sankyo, Eisai, Medtronic, Otsuka, Pfizer, Sumitomo Dainippon, Sanofi, Takeda, and Tanabe-Mitsubishi and research support from Astellas, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Eisai, MSD, Otsuka, Tanabe-Mitsubishi, and JSPS KAKENHI (grant number 25461320, PI, 2014-2016; grant number 16K09731, PI, 2016-2017). H.Y. received lecture fees from Bayer, Boehringer Ingelheim, Daiichi-Sankyo, BMS, Takeda, Otsuka, Tanabe-Mitsubishi, Medtronic, Stryker, Termo, Johnson and Johnson, and Medico's Hirata and research support from BMS. T.N. received lecture fees from Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi, Sankyo, Sumitomo Dainippon, Eisai, FP, Kyowa Hakko Kirin, Medtronic, Mochida, Nippon Boehringer Ingelheim, Novartis, Otsuka, Pfizer, Sanofi, Takeda, and Mitsubishi Tanabe. S.U. received lecture fees from Boehringer Ingelheim, Bayer, Daiichi-Sankyo, Takeda, Sumitomo Dainippon, Sanofi, Otsuka, Mitsubishi Tanabe, AstraZeneca, Shionogi, and Astellas Amgen and research support from the Japan Cardiovascular Research Foundation. K.M. received lecture fees from Bayer Healthcare, Otsuka Pharmaceutical, Boehringer Ingelheim, AstraZeneca, Pfizer, Mitsubishi Tanabe Pharma Cooperation, Japan Stryker, Kowa, Nihon Medi-Physics Co, BMS, Sawai Pharmaceutical Co., Sumitomo Dainippon Pharma Co Ltd, Medico's Hirata, Daiichi-Sankyo, Astellas Pharma, Kyowa Hakko Kirin Pharma, Inc, Sanofi, MSD, Eisai Co., Nippon Chemiphar, and Towa Pharmaceutical Co. S.Y. received lecture fees from Boehringer Ingelheim, Bayer, Daiichi-Sankyo, Pfizer, BMS, Takeda, Sanofi, Otsuka, Tanabe-Mitsubishi, Medtronic, Stryker, and Medico's Hirata and research support from BMS and Takeda. Y.O., F.S., H.K., and T. Hamasaki have no disclosures to report., (Copyright © 2021 Elsevier Inc. All rights reserved.)