BACKGROUND: Topiramate is an anticonvulsant medication commonly used for a variety of neurological disorders including migraine prophylaxis. Broadened use of topiramate has brought an increased awareness of toxicity from this medication, particularly central nervous system side effects and metabolic acidosis. OBJECTIVE: We describe a case of topiramate toxicity occurring in a 22-year-old female following the ingestion of two 200 mg tablets, which she was prescribed for the treatment of migraines. RESULTS: During her outpatient cardiology evaluation for suspected postural orthostatic tachycardia syndrome (POTS), the patient experienced flushing and anxiety. Upon transfer to our hospital she was tachycardic, hypertensive, and confused. Her autonomic symptoms were consistent with her prior episodes of autonomic instability, while the confusion was new. Admission laboratory values revealed a metabolic acidosis with a mildly elevated anion gap. A blood topiramate level returned a value of 8.4 mg/L 15 h after the ingestion. Her symptoms cleared within 24 h following admission. CONCLUSION: Clinicians should consider topiramate toxicity in their differential diagnosis for patients with neurological diseases presenting with acute-onset confusion and metabolic acidosis.