Medication errors can occur in all clinical settings, but can have especially devastating results in emergency departments (EDs). Between January 1, 2011, and December 31, 2020, 250 serious medication errors occurring in the ED were reported to the Pennsylvania Patient Safety Reporting System. Errors were more likely to occur on weekends and between 12:00 pm and midnight; patients were more likely to be women. Potential strategies to reduce serious medication errors (e.g., inclusion of emergency medicine pharmacists in patient care) are discussed.