Objective: This brief report summarizes a replication and extension of a developmental outcome modeling study, by examining whether delayed substance initiation during adolescence, resulting from universal middle school preventive interventions, reduces problematic use in young adults Ages 25 and 27, up to 14.5 years after baseline. Method: Participants were middle school students from 36 Iowa schools randomly assigned to the Strengthening Families Program plus Life Skills Training (SFP 10–14 + LST), LST-only, or a control condition. Self-report questionnaires originally were collected at 11 time points, through Age 22. A subsequent grant allowed for assessments at Ages 25 and 27, including measures of drunkenness, alcohol-related problems, cigarette use, illicit drug use (lifetime and frequency), marijuana use and prescription drug misuse. These outcomes were modeled as variables influenced by growth factors describing substance initiation during adolescence. Models included the effects of baseline risk, intervention condition assignment, and their interaction; risk-related moderation effects were examined and relative reduction rates were calculated for dichotomous variables. Results: Model fits were good. Analyses showed significant or marginally significant indirect intervention effects on all outcomes, through effects on adolescent substance initiation growth factors. Intervention × Risk interaction effects favored the higher risk subsample, replicating earlier findings. Additional direct effects on young adult use were observed only for cigarette frequency. Relative reduction rates were larger for the higher risk subsamples, ranging from 3.9% to 36.2%. Conclusions: Universal preventive interventions implemented during early adolescence have the potential to decrease the rates of substance misuse and associated problems into young adulthood.