Headache is the most frequent neurological chief complaint in the emergency room (ER). During diagnostic workup, accurate history taking still is the mainstay for identification of patients with a serious underlying disorder. However, in patients with an immigrant background, language problems and cultural influences on pain perception and pain-associated behavior can pose serious challenges for physicians. Here, we have evaluated the epidemiological characteristics of the chief complaint headache in ER patients with a probable immigrant background. We performed a retrospective study on 4,132 consecutive neurological ER patients. Identification of patients with probable immigrant background was done by a name based algorithm. Epidemiological characteristics of ER headache patients with and without probable immigrant background were evaluated. Patients with a probable immigrant background had a higher frequency of headache as chief complaint compared to age-and sexmatched control patients (32 vs. 21%). In addition, headache patients with a probable immigrant background had a lower frequency of serious causes (5.2 vs. 16%). Approximately eight cranial imaging procedures and three lumbar punctures were performed for one serious diagnosis in patients with a probable immigrant background. In control patients, these ratios were three and one, respectively. Taken together, our data suggest that socio-cultural factors such as migrational status significantly affect pain-associated behavior of headache patients as well as the clinical workup in an ER. Culturally competent care may be optimized by interpreters, standardized headache questionnaires and easy access to cranial imaging when a benign etiology cannot be firmly established.