We examined the variations of adolescent health status and risk involvement– prevalence of mental health disabilities, chronic health conditions, substance use, and exposure to tobacco–between 6 family structures in a school-based sample of Latino, Somali, Hmong, and White students and whether ethnicity moderated these associations. Data were collected from the 2013 Minnesota Student Survey, comprising a sample of 29,345 from 8th, 9th, and 11th grades. Logistic regression investigated relationships between family structure and health variables. Adolescents in nuclear families reported better health outcomes in most models; odds of mental disabilities were 1.64 for single parent and 2.45 for other family structures. Significant effect modification was noted for all health outcomes; extended families were consistently protective for Hmong youth and offered some protection for Latino and Somali youth. Policies and programs that support parents and guardians are essential, and may be especially beneficial for ethnic minority youth in single-parent, grandparent-only, and other family structures.