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Background: Wake-up stroke (WUS) accounts for up to 29.6% of ischemic strokes, but its mechanisms are poorly understood. The purpose of this study is to identify risk factors and characteristics of WUS., Methods: Seven-two ischemic strokes were classified as WUS or non-WUS. Collected were demographic information, medical history, cholesterol profile, and stroke characteristics including severity (National Institutes of Health Stroke Scale [NIHSS]) and mechanism (Trial of Org 10172 in Acute Stroke Treatment criteria). Subjects completed questionnaires screening for sleep apnea (Berlin questionnaire) and assessing sleep characteristics., Results: There were 72 ischemic strokes, of which 28 WUS (38.9%). WUS and non-WUS patients were similar in regard to stroke risk factors. WUS patients tended to be African American and were significantly younger. WUS was significantly more likely to result from small-vessel disease mechanism (42.9% versus 14.0%; P=.006) and tended to be less severe WUS (NIHSS score 3 [1, 4] versus 4 [2, 11]; P=.13) than non-WUS. Groups did not differ in regard to scoring positively on the Berlin questionnaire, but WUS sufferers were more likely to snore frequently (90.5% versus 70.0%, P=.08). The lipid profile was significantly worse in WUS compared with non-WUS (low-density lipoprotein 124.6±38.4 versus 103.7±36.8; P=.03; cholesterol to high-density lipoprotein ratio 5.2±1.6 versus 4.3±1.6; P=.02)., Conclusions: WUS is more likely to result from small-vessel disease mechanism. Poorer cholesterol profile and frequent snoring may contribute to WUS., (Published by Elsevier Inc.)