This retrospective cohort study, conducted over a 10-year period, linked hospital records and state death records to identify patients who died within 7 days of being discharged from the emergency department (ED). Approximately 30 unexpected deaths occurred per 100,000 ED discharges, and a potential error or misdiagnosis was detected in more than half of these cases. Although prior research found that both physician knowledge and system factors contributed to missed diagnoses in the ED, in this study, unexpected post-discharge deaths were more commonly associated with unusual illnesses or psychiatric or substance abuse comorbidities.