Overdosage of diphenhydramine may result in the development of anticholinergic symptoms, seizures, and coma. A fatal outcome following a diphenhydramine overdose does not commonly occur. This report describes the largest documented overdosage of diphenhydramine (7.5 g) which resulted in the death of a 14-year-old girl. The patient initially developed seizures following by cardiac conduction and hemodynamic compromise resulting in death despite life support measures.