The aim of this study was to measure prevalence, to describe underlying etiologies, and to assess radiological findings, focusing on significant intracranial abnormality (sICA). This was a prospective study of unselected adult patients admitted to the emergency department (ED) in a tertiary care hospital where all presenters were systematically interviewed about their symptoms. We attributed nontraumatic headache with neuroimaging to four groups: Normal or no new finding, extracranial abnormality, insignificant intracranial abnormality, or significant intracranial abnormality. sICA was defined as “needing acute therapy”, “needing follow-up neuroimaging”, or “clinically important neurological disorder”. Among 11,269 screened ED presentations, the prevalence of nontraumatic headache was 10.1% (1132 patients). Neuroimaging (cCT and/or cMRI) was performed in 303 patients. Seventy (23.1% of scanned; 6.2% of all headache patients) patients had sICA. Etiologies were cerebrovascular disease (56%), intracranial bleeding (17%), tumors (14%), infection (9%), and others (6%). Short-term outcome was excellent, with 99.3% in-hospital survival in patients with and 99.4% in patients without neuroimaging, and 97.1% in sICA; 1-year survival in outpatients with neuroimaging was 99.2%, 99.0% in outpatients without, and 88.6% in patients with sICA. Factors associated with sICA were age, emergency severity index (ESI) of 1 or 2, Glasgow coma score (GCS) under 14, focal neurological signs, and a history of malignancy. Prevalence of headache and incidence of sICA were high, but survival after work-up for nontraumatic headache was excellent in the 94% patients without sICA. Due to the incidence of sICA, extensive indication for neuroimaging in headache patients is further warranted, particularly in patients with risk factors.