Background and PURPOSEMigraine has been shown to increase cerebral excitability, promote rapid infarct expansion into tissue with perfusion deficits, and result in larger infarcts in animal models of focal cerebral ischemia. Whether these effects occur in humans has never been properly investigated. METHODSIn a series of consecutive patients with acute ischemic stroke, enrolled in the setting of the Italian Project on Stroke at Young Age, we assessed acute as well as chronic infarct volumes by volumetric magnetic resonance imaging, and compared these among different subgroups identified by migraine status. RESULTSA cohort of 591 patients (male, 53.8%; mean age, 37.5±6.4 years) qualified for the analysis. Migraineurs had larger acute infarcts than non-migraineurs (median, 5.9 cm3 interquartile range (IQR), 1.4 to 15.5 vs. 2.6 cm3 IQR, 0.8 to 10.1, P<0.001), and the largest volumes were observed in patients with migraine with aura (median, 9.0 cm3 IQR, 3.4 to 16.6). In a linear regression model, migraine was an independent predictor of increased log (acute infarct volumes) (median ratio MR, 1.64; 95% confidence interval CI, 1.22 to 2.20), an effect that was more prominent for migraine with aura (MR, 2.92; 95% CI, 1.88 to 4.54). CONCLUSIONs These findings reinforce the experimental observation of larger acute cerebral infarcts in migraineurs, extend animal data to human disease, and support the hypothesis of increased vulnerability to ischemic brain injury in people suffering migraine.