A 68-year-old male patient was admitted to our clinic with chronic atrial fibrillation (AF) and decreased consciousness. Diffusion-weighted magnetic resonance imaging of the brain revealed areas of high signal intensity, T2* cortical microbleeds (MBs), and cortical superficial siderosis. Cerebral amyloid angiopathy (CAA) with micro-infarction was diagnosed, and direct oral anticoagulant (DOAC) therapy was initiated. Due to increasing MBs and intracerebral hemorrhages, DOAC was discontinued. Subsequently, the micro-infarction and MBs abated, and the patient's consciousness gradually improved. Catheter ablation was performed for AF, restoring sinus rhythm. DOAC can be harmful for CAA patients with AF linked to cortical hemorrhage. Thus, it is important to discontinue DOACs for micro-infarctions in cases of CAA with AF.