Introduction: This study provides an update on mortality due to diseases of despair within the Appalachian Region, comparing 2015 to 2018. Methods: Diseases of despair include: alcohol, prescription drug and illegal drug overdose, suicide, and alcoholic liver disease/cirrhosis of the liver. Analyses are based on National Vital Statistics System (NVSS) mortality data for individuals aged 15-64. Results: Between 2015 and 2017, the diseases of despair mortality rate increased in both Appalachia and the non-Appalachian U.S.,...