Abstract: Objective To determine the associations between hyperdense middle cerebral arteries sign (HMCAS) and large vessel occlusion (LVO) and clinical outcomes in patients with acute ischemic stoke. Methods Patients who were admitted to the Stroke Center of West China Hospital of Sichuan University within 6 h after onset of acute ischemic stroke from July 2015 to July 2017 were included in this study. Logistic regression models were established to determine the value of HMCAS in predicting LVO, hemorrhagic transformation and 90-d functional outcome using the receiver operating characteristic curve. Results A total of 292 stroke patients were recruited and 50 (17.1%) presented with HMCAS, including 41 (82.0%) with confirmed as LVO. HMCAS had a value of 0.682 in the area under the receiver operating characteristic curve for predicting LVO 〔odds ratio OR)=8.93, 95% confidence interval CI): 3.72-21.48, P<0.001), better than early CT infarct (0.682 vs. 0.602, P=0.038). HMCAS was also an independent predictor for hemorrhagic transformation OR=5.32, 95%CI: 2.16-13.11, P<0.001) and poor functional recovery OR=3.02, 95%CI: 1.19-7.62, P=0.019). Conclusion HMCAS is a risk factor of large artery occlusion, hemorrhagic transformation, and poor functional recovery in patients with acute ischemic stroke.