This study examines the association of individual and familial risk factors with exposure to trauma and posttraumatic stress disorder (PTSD) in male twins (N = 6744) from the Vietnam Era Twin Registry. Independent reports of familial psychopathology from co-twins were used to avoid the potential biases of the family history method. Risk for exposure to traumatic events was increased by service in Southeast Asia, preexisting conduct disorder, preexisting substance dependence, and a family history of mood disorders whose effects appear to be partly genetic. Preexisting mood disorders in the individual were associated with decreased odds of traumatic exposure. Risk of developing PTSD following exposure was increased by an earlier age at first trauma, exposure to multiple traumas, paternal depression, less than high school education at entry into the military, service in Southeast Asia, and preexisting conduct disorder, panic disorder or generalized anxiety disorder, and major depression. Results suggest the association of familial psychopathology and PTSD may be mediated by increased risk of traumatic exposure and by preexisting psychopathology.