The authors examined competing hypotheses regarding the role of 2 personality dimensions, disconstraint and negative emotionality, in mediating the relationship between posttraumatic stress disorder (PTSD) severity and substance-related problems. Data were drawn from a large sample of male Vietnam veterans. The best-fitting structural model included significant indirect paths from PTSD to both alcohol- and drug-related outcomes through disconstraint, and a significant indirect path from PTSD to alcohol-related problems through negative emotionality. There were no direct effects of PTSD on either substance-related outcome. These findings indicate distinct pathways to different forms of substance-related problems in PTSD and underscore the role of personality in mediating these relationships.