BACKGROUND AND PURPOSE - : The study aimed to assess whether onset headache is an ominous sign in patients with first-ever ischemic stroke. METHODS - : A large population of ischemic stroke patients was obtained from the Taiwan Stroke Registry. Stroke subtypes were classified by the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria. On the basis of the International Classification of Headache Disorders, second version, onset headache was defined as a new headache that developed at the onset of ischemic stroke. Clinical features and impact on stroke outcomes, including in-hospital stroke in evolution, changes in National Institutes of Health Stroke Scale on discharge, and Barthel index and modified Rankin scale ≤6 months after stroke were compared between those with and without onset headache. RESULTS - : Among 11 523 patients with first-ever ischemic stroke, 848 had onset headache (7.4%). Patients with specific cause, large-Artery atherosclerosis, or cardioembolism were more likely to have onset headache. Patients with onset headache were younger, predominantly female, and more likely to have posterior circulation ischemic lesions. Compared with patients without onset headache, those with onset headache had a lower frequency of stroke in evolution (4.5% versus 6.7%; adjusted relative risk, 0.64; 95% confidence interval, 0.52-0.79), greater improvement in National Institutes of Health Stroke Scale score on discharge (0.08 versus -0.20; P=0.02), higher mean Barthel index scores (86.5±20.0 versus 83.9±23.3; adjusted difference, 1.43; 95% confidence interval, 0.28-2.89), and a lower frequency of modified Rankin scale higher than 2 (27.6% versus 31.5%; adjusted relative risk, 0.85; 95% confidence interval, 0.72-0.95) at 1-month follow-up. There was also a trend for better functional outcome in 3- and 6-month follow-ups. CONCLUSIONS - : By adopting standard classification criteria, this large-scale study demonstrated that onset headache was associated with modest but significantly better outcomes after ischemic stroke.