The five factor model of personality is a useful metric to describe personality profiles associated with maladaptive functioning. Using the NEO-Five Factor Inventory (NEO-FFI), we examined a conceptually based profile of high neuroticism, low agreeableness and low conscientiousness among 243 youth (aged 13-18 years) with varying degrees of conduct disorder (CD) and substance use disorders (SUD). Comparisons of the NEO-FFI personality dimensions between CD/SUD youth and adolescent siblings (N=173), and relations between the personality dimensions and behavioral indicators of conduct disorder and substance involvement were examined. Youth with CD and SUD had greater neuroticism, lower agreeableness, and lower conscientiousness than siblings of a similar age. The NEO-FFI scales predicted aggression and substance involvement for both probands and siblings in this cross-sectional investigation. These findings support the role for personality in models of the etiology and persistence of conduct disorder and substance use disorders.