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Background and purpose: paroxysmal AF is detected during follow-up in approximately 30% of ESUS. We aim to identify patterns of brain lesions suggestive of embolic events and to evaluate the incidence of AF during 4-years of follow-up.Design and method: acute ischemic stroke patients were prospectively included in a multidisciplinary secondary stroke prevention program. Cardioembolic stroke was ruled out with 12-lead ECG, 48-hour cardiac monitoring and transesophageal echocardiography. Large artery disease of intracranial and extracranial vessels was evaluated with MR or CT angiography or cervical duplex plus transcranial doppler ultrasonography. After this thorough evaluation, patients without cardioembolic or large artery disease and non-lacunar lesion on MRI were defined as ESUS.Results: 479 (34%) of 1376 ischemic strokes included from September 2009 to December 2016 were ESUS; median age 78 years (IQR 69-84), 55% female. Pre-stroke VRF profile: 80% HT, 66% dyslipidemia, 14% DM, 51% obesity, 39% smoking, 34% CKD, 3% history of paroxysmal AF, 14% CHD and 10% previous stroke or TIA. Twenty-four patients (5%) died during hospitalization or within the next 30 days. There were 25 % (CI 95% 22-29) of recurrent strokes during 4-years of follow-up after stroke. The AF was detected in 15% of patients in the first year, 28% in the second year, 38% in the third year and 41% in the fourth year. Neuroimaging findings on-admission MRI are shown in the table.Conclusion: ESUS patients with AF during follow-up had higher incidence of hemorrhagic transformation during the acute phase as well as multiple lesions in different territories of the anterior and posterior cerebral circulation. As these findings are often seen in strokes of indubitable embolic origin the presence of these features should raise the suspicion of an underling embolic source.