Background and objectives To assess the usefulness of the “index vein” for making the diagnosis of migraine aura. Methods 400 patients were included when they: i) presented with an acute neurological deficit, ii) had a brain MRI, and iii) had a discharge diagnosis of migraine aura, ischemic stroke, epileptic seizure or controls (n = 100 per group). Results Compared to stroke (2%), epileptic seizure (4%) and controls (1%), the index vein is more prevalent in migraine aura (17%, p < 0.001). The index vein is highly specific for migraine aura (specificity 97%, 95% CI 95–99). The index vein has a positive predictive value for the diagnosis of migraine aura of 70% (95%CI 48–87). The index vein-score has the ability to diagnose migraine aura with a sensitivity of 94% (95%CI 87.4–97.8) and specificity of 73.5% (95%CI 66.8–79.5) at a cut-off of 4 points. Discussion The index vein serves as a good biomarker for migraine aura in the emergency setting.