Valproic acid (VPA) is a wide spectrum antiepileptic medication indicated for seizure prophylaxis across the spectrum of epilepsy. Since coming into clinical use, VPA has also been recommended for the management of a variety of other pathologies, including, most notably, mood stabilization in the manic patient. VPA’s common adverse effects include gastrointestinal, influenza-like symptoms, headache, and difficulties with sleep; nonetheless, in rare instances, VPA has been noted to cause the severe and potentially lethal condition of hyperammonemia with encephalopathy (VIHE). VIHE is the result of a dose-independent increase in ammonia levels. Often the patient is asymptomatic; if symptoms reach clinical threshold, lethargy is most common, though seizures, focal neurologic deficits and even coma are possible. VIHE can occur in patients despite normal hepatic function, normal loading doses, chronic stable doses and normal free serum drug levels. Once the diagnosis is confirmed, the first approach for symptomatic patients is to discontinue VPA, start alternative mood stabilizer as indicated, and supplement hyperammonemia treatment with lactulose, carnitine or carglumic acid. Below is a case report of VIHE that developed in an adolescent girl with a history of Bipolar I Disorder who was hospitalized in our facility for stabilization of mania. As demonstrated below, early diagnosis of VIHE is pivotal in reducing morbidity and ultimately can be life-saving. Keywords: Valproic acid, Hyperammonemia, Encephalopathy