Since its initial formulation, the biosocial theory of borderline personality disorder (BPD) still lacks robust empirical evidence, given there are no prospective longitudinal studies testing the main assumptions of the model. The current study examined longitudinally whether temperamental traits harm avoidance (HA) and novelty seeking (NS), internalizing and externalizing disorders, trauma and perceived invalidating parenting style, as measured during adolescence, contributed to the risk of BPD, diagnosed on the basis of standardized clinical interviews 5 years later. Individuals with BPD (n = 17) from a community sample of 416 young adults were compared to individuals with depressive disorders (n = 17) and psychiatrically healthy subjects (n = 34). Results indicated that adolescent internalizing disorders as well as the interaction of HA and perceived maternal overprotection predicted the risk of BPD 5 years later. NS was not shown to be a predisposing vulnerability. Results are interpreted as confirmation of the biosocial model. Gender-specific etiological differences are discussed. Copyright © 2010 John Wiley & Sons, Ltd.