Managing acutely agitated or violent patients in the emergency department (ED) represents a significant challenge. Acute agitation as an initial manifestation of neuro-Behcet's disease (NBD) is an extremely rare clinical entity. A 44-year-old male, who had been complaining about a severe headache and fever for several days, was admitted to our ED due to acutely presented incontinence and agitation. On admission, physical restraint and sedation with sevoflurane and propofol were required for his combative and violent behavior. Cerebrospinal fluid examination revealed increased cell count. Fluid attenuated inversion recovery magnetic resonance imaging showed a high intensity signal in the left parietal lobe and bilateral occipital lobe. As infectious meningoencephalitis was suspected, empirical therapy was immediately started. He recovered uneventfully without neurological defect in seven days. Based on positive human leukocyte antigen B-51 and clinical manifestations, the diagnosis of NBD was made and remitted by steroid therapy. Although acute NBD commonly presents with focal neurological symptoms, psychiatric symptoms could be considered the first manifestation. A focused and thorough examination coupled with appropriate management strategies can assist emergency clinicians safely and effectively manage these patients.