This study tested a mediation model of the relationship with tobacco use, social network quality (level of risk or protection in a network), and substance use (alcohol and/or illicit drugs) with a sample of 301 urban adolescents. It was theorized that social network quality would mediate the effect of tobacco use, accounting for PTSD symptoms and parent-teen relationships, on substance use. Results of path modeling with AMOS showed that the model provided an overall very good fit to the data and demonstrated partial mediation effects of social network quality on substance use. An effect-size measure was applied to determine what proportion of the total effect was mediated by the intervening (social network) variable and produced a moderate effect size (0.31). Results highlight the mediating role of social network quality on risk factors for adolescent substance use and are informative to prevention science in advancing social operational models of substance use. (Contains 1 table and 2 figures.)