Introduction: Acute ischemic stroke (AIS) is a devastating complication of COVID-19 with high morbidity and mortality. In this study, we reported the frequency, characteristics, and outcome of AIS in patients with COVID-19. Methods: This multicenter and cross-sectional study was conducted between April 2020 and February 2021. Among the hospitalized patients with COVID-19, the detailed characteristics of those with and without AIS were recorded and compared. Results: Six hundred ninety-three patients were included in the study. Acute ischemic stroke was detected in 16 (2.31%) patients, the median age was 77 (range, 48–91) years, and 10 (62.5%) were female. The median NIHSS score at admission was 9 (range, 3–17). Total anterior circulation infarction (TACI) was the most common (37.5%) type and cardioembolism was the most common etiology (37.5%). Nine patients (56.25%) developed AIS within 24 hours of having COVID-19. COVID-19 severity was severe or critical in seven patients (43.75%). Eight patients died, and eight were discharged. Patients with AIS had a higher rate of hypertension, coronary artery disease, heart failure, a history of myocardial infarction, a history of cerebrovascular disease, severe and critical COVID-19, a higher mean age, and a longer ICU stay compared with those without AIS (p<0.001 for each). Conclusions: AIS can occur in patients with COVID-19 and is associated with mortality. Acute ischemic stroke is encountered at any stage of COVID-19, especially within the first 72 hours of the diagnosis, in older patients with comorbidities and severe COVID-19. There is an increased risk of AIS in patients with COVID-19 with a history of stroke.