This longitudinal study examined familial and child predictors of academic achievement and behavioral adjustment. Participants included 115 children with ADHD and 59 normative comparisons. Data analyses spanned three assessment waves from elementary- through secondary-school grades. We evaluated the degree to which child and familial factors present during middle school mediated relationships between childhood ADHD, subsequent academic achievement and behavioral adjustment during high school. We found that emotional and behavioral well-being of ADHD children during middle school mediated relations between childhood ADHD and adverse academic and behavioral outcomes during high school. In addition, familial factors in middle school years predicted the behavioral adjustment of children in both the ADHD and non-ADHD groups. Academic achievement during high school was strongly associated with previous achievement levels. Our results provide support for tailoring preventive interventions to the unique needs of children with ADHD and their parents at various stages of adolescent development.