Based on Jessor’s problem behavior theory (PBT; R. Jessor, 1987, Problem-behavior theory, psychosocial development, and adolescent problem drinking, British Journal of Addiction, Vol. 82, pp. 331–342), the comparability of a second-order problem behavior model (SPBM) was investigated employing structural equation modeling (SEM) and latent mean differences in problem behavior engagement were examined among racial/ethnic adolescents. Within a span of nearly 25 years, this study represents the first nationally representative sample of Latino and African American adolescents utilized in testing Jessor’s PBT and problem behavior syndrome (PBS). Using a sample of 5,831 Latino, African American, and European American adolescents drawn from the National Longitudinal Study of Adolescent Health, a series of invariance tests evidenced support for Jessor’s PBT and PBS. Latent mean difference test results evidenced significant differences in problem behaviors (e.g., academic failure [AF], aggression [AG], substance use [SU], and risky sexual activity[RSA]) across racial/ethnic adolescent groups, which could be explained partially by PBS. A discussion of findings, limitations, and recommendations for future research is presented.