The well-documented association between combat-related PTSD (C-PTSD) and other mental disorders may be an artifact of shared familial vulnerability. This study uses a co-twin control design to examine whether the association between C-PTSD and other mental disorders persists after adjusting for shared familial vulnerability. Data were from male monozygotic twin pairs in the Vietnam Era Twin Registry. Logistic regression analyses demonstrated that combat exposure, adjusted for C-PTSD, was significantly associated with increased risk for alcohol and cannabis dependence and that C-PTSD mediated the association between combat exposure and both major depression and tobacco dependence. We conclude C-PTSD comorbidity persists after controlling for shared vulnerability. Combat exposure is directly and indirectly, through C-PTSD, associated with increased risk for other mental disorders.