Substance abuse is one of the most problematic health risk behaviors among adolescents. Given that research consistently finds increased levels of substance use among adolescents with conduct problems as well as trauma-related symptoms, it is important that substance abuse be examined to better understand its role in Conduct Disorder (CD) and Post-Traumatic Stress Disorder (PTSD). This study further explored whether these relationships were better understood with additive and interactive processes. Adolescents (N = 192) admitted to a psychiatric inpatient unit completed a standard intake evaluation, including checklists and a semi-structured interview. Levels of substance abuse were greater for those with comorbid CD and PTSD as compared with either CD only or PTSD only. This difference was best explained by interactive rather than additive processes. Therefore, treatment implications are discussed.