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Objective: To analyze the relationship between carotid plaque vulnerability on contrast-enhanced carotid ultrasound (CEUS) and underlying stroke pathogenesis in acute cerebral infarction.Methods: Patients from Beijing TianTan hospital, who suffered from acute cerebral infarction in anterior circulation, attributing to intra/extracranial large artery atherosclerosis, were enrolled. Infarction imaging characteristics were evaluated on diffusion weighted imaging sequence with brain MRI and vulnerable plaques were assessed with CEUS within 14 days since the onset of the symptoms. Participants also attended a follow-up after 90±7 days. Logistic regression was used to analyze the relationship between plaque vulnerability and imaging characteristics. Survival analysis was performed to evaluate the predictive effects of vulnerable plaques on ischemic stroke relapse.Results: Between October 2015 and December 2016, a total of 93 patients were enrolled. Vulnerable plaque was found in 35 (37.6%) participants on CEUS and was an independent risk factor of embolization (odds ratio [OR], 3.63; 95% confidence interval [CI], 1.19-11.12; P=0.02), especially in patients without intracranial large artery atherosclerosis (odds ratio, 5.67; 95%CI, 1.36-23.67; P=0.02). However, this relationship was not found when plaques were detected with traditional carotid ultrasound. When analyzing with single-factor Kaplan-Meier curve, vulnerable plaque on CEUS was also an indicator of stroke relapse within 3 months (P=0.04).Conclusion: For patients with acute cerebral infarction attributing to atherosclerosis, compared to carotid ultrasound, CEUS is more precise when assessing the vulnerability of the plaques. Vulnerable plaque on CEUS is associated with stroke mechanisms and prognosis, which may provide more evidence for making appropriate secondary prevention plans.