Background: The association between migraine and the incidence of ischemic stroke varies in different subgroups of patients. We aimed to clarify this association using a population-based database. Method: A nationwide cohort study was conducted using data from the Taiwan National Health Insurance Research Database. Two cohorts were extracted: a neurologist-diagnosed migraine cohort, and a non-headache, propensity score-matched comparison cohort. All participants were enrolled in this study between 2005 and 2009, and were followed through the end of 2010, death, or the occurrence of ischemic stroke. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were calculated with a Cox proportional hazards model to compare the between-group risks. Results: Both cohorts (n=119,017 each) were followed for a mean period of 3.6 +/- 1.3 years. A total of 744 migraine patients (429,741 person-years) and 617 matched comparison individuals (436,141 person-years) developed ischemic stroke during the research period. Compared to the comparison cohort, patients with migraine were at an increased risk of ischemic stroke (aHR: 1.24, 95% CI: 1.12-1.38, p<0.001). Subgroup analysis by age and sex revealed the highest risk in women aged <= 45 years (aHR: 3.44, 95% CI: 2.20-5.39, p<0.001), especially among those with migraine with aura (aHR: 4.58, 95% CI: 2.45 - 8.56, p<0.001). A trend for increased stroke risk was observed in men aged <= 45 years (aHR: 1.54, 95% CI: 0.96-2.48, p=0.075). Conclusion: Migraine is associated with an increased risk of ischemic stroke, especially in younger (age <= 45 years) women with migraine with aura. The trend toward ischemic stroke in younger men merits further exploration.