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Background and objectives: There is limited data on the optimal times to start anticoagulation (AC) in patients with a recent ischemic stroke. The objective of this pilot study was to investigate the safety of our institutional MR imaging based paradigm (MR-IBP, Figure) regarding initiation of AC in acute ischemic stroke patients, with and without large ischemic stroke.Methods: Patients admitted with acute ischemic stroke between July 1, 2014 and December 31, 2015 and consented to our natural history protocol were included in this study. Eligible patients had a discharge diagnosis of ischemic stroke and were started on AC during their acute hospitalization. We rated all incidences of hemorrhagic transformation (HT) using ECASS-II criteria during their acute hospitalization with the HT ratings performed at the time of discharge. We retrospectively evaluated all cases for large stroke based on baseline diffusion-weighted imaging (DWI) lesion diameter > 5 cm measurements.Results: Fifty-seven patients were included with 44% (25/57) started on AC according to the MR-IBP, Figure. For the patients started on AC, 8% (2/25) had HT (1 had HI-1; 1 had PH-2) after AC was started while 8% (2/25) were started on AC 1 day after HT (both were HI-2). Both patients started on AC after HT had baseline DWI lesion volumes < 1/3 MCA. Overall 16% (4/25) had HT pre- or post-AC versus patients who were not started on AC who had HT 19% (6/32) (p=0.77). There were 14 patients (25%) with large ischemic stroke. Of these large stroke patients, 8 (57%) had no HT, 4 (67%) were not started on AC but had HT post stroke (3 had HI-2; 1 had PH-1) and 2 (33%) were started on AC within MR-IBP but had HT (1 had HI-1; 1 had PH-2).Conclusion: Based on our pilot study, starting AC in patients with acute ischemic stroke including those with large stroke per our institutional MR-IBP is safe based on the low incidence of HT, with a 4% incidence of PH-2 HT during the acute hospitalization.