Purpose <p>This study examines the associations between childhood parental death and parental substance-related problems and DSM-5 substance use disorders (SUDs), suicide attempt, and mental health discorders (mood, anxiety, post truamatic stress) in adulthood..</p> Methods <p>Using data from the National Epidemiologic Survey of Alcohol and Related Conditions-III (<i>n</i> = 36,309), we compared four mutually exclusive groups who experienced the following before age 18: parental death and no parental substance use problems; parental substance use problems and no parental death; both parental death and parental substance use problems; and neither parental death nor substance use problems. We examined differences in adverse childhood experiences (ACEs), suicidality, and six DSM-5 SUD and mental health disorders. Parental death and parental substance-related problems were treated as exposures rather than included in the ACEs measure.</p> Results <p>Parentally-bereaved individuals who experienced parental substance-related problems reported significantly greater number of ACEs (M = 5.34) compared to all other groups. Parentally-bereaved individuals who experienced parental substance-related problems had greater odds of a suicide attempt and all six DSM-5 SUD and mental health disorder outcomes (aOR range = 2.06–3.59) compared to parentally-bereaved individuals without parental substance-related problems. They also had greater odds of a suicide attempt and four DSM-5 SUD and mental health disorders (aOR range = 1.19–1.46) compared to those who experienced parental substance use problems and no parental death. Some differences were attenuated in models adjusting for ACEs; however, differences remained for six of the seven outcomes.</p> Conclusion <p>Individuals who experienced parental death and parental substance-related problems have increased risk for suicidality, DSM-5 SUD, and mental health disorders which may warrant additional trauma-informed mental health care in bereavement services.</p>