We examined whether borderline personality disorder (BPD) and antisocial personality disorder (APD) could be differentiated based on defense mechanisms as measured by observer (Defense-Q; MacGregor, Olson, Presniak, & Davidson, 2008) and self-report (Defense Style Questionnaire; Andrews, Singh, & Bond, 1993) measures. We conducted 2 studies whereby nonclinical participants were divided into borderline and antisocial groups based on scores from the Personality Assessment Inventory (Morey, 1991). Multivariate analysis of variance results revealed significant overall group differences in defense use. Univariate analyses further showed group differences on several individual defenses (e.g., acting out, denial, and turning against self). Together, the findings suggest that in BPD, the defenses may emphasize interpersonal dependency and a tendency to direct aggression toward the self; whereas in APD, the defenses may emphasize egocentricity, interpersonal exploitation, and a tendency to direct aggression toward others. Overall, this study demonstrates important differences in defense use between borderline and antisocial personality groups across both observer and self-report measures.