Objective. - To describe the characteristics of headache related to lacunar stroke based on data collected from a prospective hospital-based stroke registry over a 12-year period. Demographics, clinical variables, and prognostic features of lacunar stroke in patients with and without headache are compared. Background. - Stroke-related headache has been largely investigated, but there is little clinical data on headache in individualized stroke subtypes. Methods. - The cohort of 484 patients with lacunar infarction was selected. Forty-five (9.3%) presented headache within a 72-hour interval of stroke onset. Predictors of lacunar infarction with headache were assessed by logistic regression analysis. Results. - The intensity of headache was mild in severity and poorly localized (diffuse or bilateral headache). Tension-type headache was present in 36 patients (80%) and 9 patients (20%) presented nausea or vomiting while experiencing mild pulsating pain. The frequency of headache was 17% in patients with atypical lacunar syndrome, 12% in dysarthria-clumsy hand, 11.5% in pure sensory stroke, 9.4% in sensorimotor stroke, and 7.1% in pure motor hemiparesis. When patients with lacunar infarction with and without headache were compared, female sex, diabetes mellitus, nausea and vomiting, and mesencephalic topography were significantly more frequent and dysarthria and frequency of symptom free at discharge were less frequent in the headache group. In the multivariate analysis, mesencephalic topography (odds ratio [OR] 16.62), nausea and vomiting(OR 13.27), sex female(OR 2.29), diabetes mellitus (OR 1.96), and age (OR 0.95) were predictors of lacunar infarction with headache. Conclusions. - Headache at the onset of a lacunar infarction is uncommon. Mesencephalic topography, nausea and vomiting, female sex, diabetes, and age were independent variables significantly associated with lacunar infarction with headache. These findings contribute to knowledge of stroke-related headache in patients with lacunes.