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Objectives: The lesion topography of medullary infarction (MI) is heterogeneous and its correlation with stroke etiology remains elusive. We aim to clarify the lesion pattern of MI and to assess its correlation with stroke etiology.Material and Methods: Of 1129 subjects with available DWI in SMART study (a multi-center trial concerning secondary stroke prevention in China) between April 2008 and December 2010, 43 patients with DWI confirmed MI (3.8%) were retrospectively evaluated. Lesions were categorized as lateral and medial medullary infarction (LMI and MMI, 33 and 10 subjects respectively) at 3 levels rostro-caudally and correlated with the stroke etiology. Clinical profiles and long-term prognosis were analyzed.Results: Large artery atherosclerosis, small vessel occlusion, cardiogenic embolism and artery dissection accounted for 29, 11, 1, and 2 infarcts, respectively. Large artery disease was the most common cause in LMI (24 of 33, 72.7%) whereas small vessel occlusion was not uncommon in MMI (5 of 10, 50.0%). Though the difference of infarct pattern between large artery atherosclerosis and small vessel occlusion was insignificant, two distinct lesion patterns were considered to be relevant: (1) Rostral MMI with continuous medial pontine infarctions were more likely attributed to small vessel occlusion than large artery atherosclerosis. Kameda et al. (2) MMI with ventral to dorsal extension were more often caused by large artery disease than small vessel occlusion. Median NIHSS at admission was 4. During a median follow-up of 17 months, 2 patients died and 2 experienced recurrent ischemic events, 39 of 41 subjects (95.1%) were functional independent (mRS 0–2).Conclusions: This multi-center study demonstrates that MI has distinct lesion pattern depending on various stroke etiologies and mechanisms. Future investigations with larger sample size should establish the lesion pattern of MI and validate its correlation with the stroke etiology and mechanisms, which might improve stroke management.