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Background and Purpose: After ischemic stroke (IS) or transient ischemic attack (TIA), use of an antithrombotic agent to prevent recurrence is mandatory. However, antithrombotic agents rarely cause intracranial hemorrhage (ICH), frequently resulting in worse outcomes than recurrent IS. Cerebral microbleeds (CMBs) have been reported as a useful marker for finding ICH-prone patients. This retrospective study aimed to investigate the significance of CMB in the development of ICH in first-ever IS/TIA patients.Methods: The data source was our consecutive patient registry between 2005 and 2015. Patients with stroke/TIA admitted to our hospital more than twice (first as first-ever IS/TIA and second or later as recurrent IS/TIA or ICH) and underwent head MRI including T2*-weighted imaging on the first admission were extracted. Clinical characteristics including use of antithrombotic therapy and distribution of CMB on the first and second admissions were compared between recurrent IS/TIA and ICH groups. Distribution of CMB was divided into deep, lobar, or both.Results: In total, 708 IS/TIA patients (second stroke: 640 IS/TIA; 68 ICH) were extracted. The ICH group showed a longer period until second stroke (1,062 days vs. 817 days, p=0.022) and higher mean NIHSS score (14.8 vs. 6.1, p<0.001) on second admission than the IS/TIA group. On first admission, the ICH group had a higher frequency of CMB (72.1% vs. 49.5%, p<0.001) and lower frequency of cardioembolism (14.7% vs. 25.8%, p=0.044) than the IS/TIA group. About half of hemorrhages occurred in similar locations of the CMB depicted on first admission. A higher frequency of ICH was observed in patients with deep CMB (11.3% vs. 5.6%, p=0.022) or both deep and lobar CMBs (17.4% vs. 5.6%, p<0.001) than in those without CMB. Use of anticoagulants was a significant risk factor for transition from first IS/TIA to second ICH (odds ratio [95% confidence interval]: 3.75 [1.30-10.8], adjusted by sex, age, type of first stroke, and CMB location).Conclusions: This study found IS/TIA patients with CMB are at high risk of ICH compared to patients without CMB. Preventive antithrombotic treatment particularly use of anticoagulants for CI/TIA patients with CMB should be provided under careful monitoring for the risk of hemorrhage.