The purpose of this study was to explore whether adolescents (N = 10,287) could be classified into homogeneous subgroups based on their protective factors and, if so, whether these constellations of protection differentially relate to adolescents' lifetime and 30-day alcohol and tobacco use. Latent class analysis with eight protective factors--four internal and four external--were used to identify the underlying latent class structure. Five profiles of protection emerged: Adequate Protection (54%), Adequate External Protection (9%), Adequate Protection with Low Adult Communication (16%), Adequate Protection with Risky Friends (9%), and Inadequate Protection (12%). Lifetime alcohol use was associated with only a modest increase in odds of belonging to the Adequate External or Low Adult Communication latent classes, but an enormous increase in odds of having Inadequate Protection or Risky Friends. Similar effects were found for past month alcohol use. Unlike alcohol use, which was related most strongly with membership in the Risky Friends latent class (relative to Adequate Protection), cigarette use was most strongly related to membership in the Inadequate Protection latent class. Findings can be used to inform prevention programs as they illustrate the relationships that exist between adolescents' profiles of protection and substance use.