Topiramate is used to treat a variety of neurologic and psychiatric diseases due to its benign safety profile. Data regarding the toxicity and toxicokinetics of topiramate in acute overdose are limited. A case of massive, acute ingestion resulting in the highest reported topiramate level is presented, including toxicokinetic evaluation. A 37-year-old woman presented with coma unresponsive to naloxone following topiramate ingestion. She had normal vital signs without respiratory depression. She was intubated for airway protection, given 3.5 mg lorazepam IV for facial and neck muscle twitching, and transferred to our facility. No additional sedation was required for 18 h on the ventilator. Following mental status improvement, the patient was extubated. Confusion, dysarthria, and imbalance resolved over the next 2 days. Nonanion gap metabolic acidosis persisted for 3 days. Peak serum topiramate level was 356.6 microg/ml (reference range, 5-20 microg/ml). Massive topiramate ingestion led to prolonged coma with normal vital signs and nonanion gap metabolic acidosis. Coma of this severity has not been previously reported. Serum half-life, which has not been studied after overdose, was 16 h. Despite the large ingestion and significant presenting symptoms, the patient recovered fully with supportive intensive care alone. Massive acute topiramate ingestion may lead to nonanion gap metabolic acidosis and prolonged coma which resolves with intensive supportive care. Toxicokinetic data following large, suicidal ingestion of topiramate were similar to previously published pharmacokinetic information.