Background: Acute ischemic stroke (AIS) is rare in children, and diagnosis is often delayed. Neurological involvement may occur in multisystem inflammatory syndrome in children (MIS-C), but very few cases of AIS in patients with MIS-C have been reported.Patient Descriptions: We two patients with AIS presenting with large vessel occlusive disease in previously healthy adolescents recently exposed to SARS-CoV-2 infection.Results: Both patients were subsequently diagnosed with and treated for MIS-C. Here, we discuss the course of their treatments and clinical responses.Conclusion: Early recognition and diagnosis of AIS with large vessel occlusion in children with MIS-C is critical to make available all treatment options to improve clinical outcomes. [ABSTRACT FROM AUTHOR]