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Background: Anticoagulant treatment with a vitamin K antagonist (VKA) has been reported to be associated with no major artery occlusion and small infarct volume. However, the effect of direct oral anticoagulant (DOAC) therapy on stroke volume or the site of arterial occlusion in acute ischemic stroke (AIS) patients is not well known.Methods: From March 2011 through July 2016, consecutive patients with AIS in the middle cerebral artery territory and non-valvular atrial fibrillation (NVAF) who underwent MRI were recruited. The infarct size was assessed by ASPECTS score on DWI, and the arterial occlusion site was evaluated on MR angiography. The effect of prior DOAC treatment on the site of arterial occlusion was assessed by multivariate ordinal logistic regression analysis.Results: A total of 345 patients (160 women; median age 79 years; median NIHSS score 12) were enrolled. Of these, 248 were on no anticoagulant, 45 were undertreated with a VKA, 24 were sufficiently treated with a VKA, and 28 were on a DOAC prior to the AIS. The DWI-ASPECTS on admission differed among the groups (median 7 in patients with no anticoagulant, 8 in undertreated VKA, 9 in sufficient VKA, and 9 in DOAC, p=0.002). Multivariate analysis showed that prior DOAC treatment was independently and negatively associated with more proximal artery occlusion (OR 0.39, p=0.031), compared to no anticoagulant.Conclusion: DOAC treatment prior to the event was associated with decreased risk of more proximal artery occlusion in AIS patients with NVAF, compared to no anticoagulation.