Stroke has potentially devastating consequences for patients receiving veno-arterial extracorporeal membrane support (VA-ECMO). Arterial cannulation sites for VA-ECMO include the ascending aorta, axillary artery, and femoral artery. However, the influence of cannulation site on stroke risk has not been well described. The purpose of this study was to investigate the association between occurrence and patterns of stroke with ECMO arterial cannulation sites. We retrospectively reviewed 414 consecutive patients who received VA-ECMO support for cardiogenic shock between March 2007 and May 2018. Patients were categorized by cannulation strategy. The rates, subtype and location of strokes as assessed by neuroimaging during and after VA-ECMO support were analyzed. Median age was 61years (IQR 50–69); 67% were men. 77 patients were cannulated via the ascending aorta (17%), 31 via the axillary artery (7%), and 306 (69%) via the femoral artery. In total, 26 patients (6.3%) developed 30 stroke lesions at a median of 6.0 (IQR 3.1–8.7) days after ECMO cannulation. Ischemic stroke was the most common subtype (64%), followed by hemorrhagic transformation (20%) and hemorrhagic stroke (16%). Location by CT was right hemispheric in 38%, left hemispheric in 24%, bilateral in 21%, and vertebrobasilar in 17%. The incidence of stroke was similar across cannulation strategies: aorta (n = 5, 6.5%), axillary artery (n = 2, 6.5%), and femoral artery (n = 19, 6.2%), (p = 0.99). Incidence of stroke does not appear to differ among patients cannulated via the ascending aorta, axillary artery, or femoral artery. Ischemic stroke was the most common subtype of stroke.