N-acetylcysteine is the established treatment for acetaminophen toxicity. This medication's complex dosing schedule engenders a high incidence of medication errors. While nuisance side effects are common, only rare case reports describe serious outcomes associated with N-acetylcysteine administration, all of which take place in the setting of non-intentional N-acetylcysteine overdose. This case report contributes to a small but growing literature that suggests that large N-acetylcysteine overdose may have devastating outcomes. We describe a 15-year-old female who presented with stage III acetaminophen toxicity and who received a non-intentional 6-fold overdose of intravenous N-acetylcysteine due to a medication prescribing error. During the N-acetylcysteine infusion dosing error, the patient had clinical deterioration including seizure followed by cerebral edema and brain herniation that progressed to brain death. She developed agitation and worsening headache within 2 h of the dosing error, which progressed to seizure and intubation 14 h into the dosing error. Although possibly due to hepatic encephalopathy, at the time she developed fixed dilated pupils, her lactate, international normalized ratio, aspartate aminotransferase, and alanine aminotransferase had all improved. On review of the literature, other case reports of seizures (n = 4) and cerebral edema with brain herniation (n = 3) were found, suggesting our patient was not an isolated case. Clinicians need to be aware of the common occurrence of dosing errors for N-acetylcysteine infusions. We suggest institutions review their N-acetylcysteine ordering, dosing, and mixing protocols in order to avoid similar rare errors in the future. Iatrogenic overdose of N-acetylcysteine can cause seizure, cerebral edema, and brain death.