This research tested the relation of socioeconomic status (SES), indexed by parental education, to stress-coping variables and substance use in a sample of 1,391 adolescents. Lower education was related to higher level of adolescent substance use, lower levels of protective factors, and higher levels of risk factors. Mediation analyses indicated that the effect of education on adolescent substance use was mediated through relationships to parental support, academic competence, behavioral competence, negative life events, and friends' substance use. Moderation analyses indicated that adolescents from lower education families were more vulnerable to risk factors but also derived more benefit from protective factors. Multiple-group analysis indicated that moderation was attributable to larger paths in the lower education group for negative events and friends' use. Implications for the relation between SES and health risk are discussed.