Objectives: Vertigo is a common presenting complaint resulting from central or peripheral etiologies. Because central causes may be life-threatening, ascertaining the nature of the vertigo is crucial in the emergency department (ED). With a broad range of potential etiologies, distinguishing central causes from benign peripheral causes is a diagnostic challenge. Cranial magnetic resonance imaging (MRI) is the recommended neuroimaging method when clinical findings are ambiguous. However, MRI scanning for every patient with an uncertain diagnosis may not be efficient or possible. Therefore, to improve ED resource utilization for patients with vertigo, there is a need to identify the subset most likely to have MRI abnormalities. It has previously been shown that S100B protein provides a useful serum marker of stroke, subarachnoid hemorrhage, and traumatic brain injury. This study evaluated whether S100B levels could predict central causes of vertigo as identified by cranial MRI in the ED.