This study was designed to test the efficacy of Parents Who Care (PWC), a seven-session universal prevention program which includes parenting, youth, and family components designed to prevent substance use and other problem behaviors. Using an intent-to-treat experimental design, this study tests the program efficacy across race within a balanced sample of European American (EA) and African American (AA) youth and their parents (n = 331 n AA = 163; n EA = 168). Families were recruited, randomly assigned to three conditions (group-administered [PA], self-administered with telephone support [SA], and no-treatment control) and the intervention was administered when the adolescents were in the eighth grade. Analyses on key teen outcomes of the Parent's Who Care program at 24-month follow-up are reported here and include perceptions of drug use harm; favorable attitudes about drug use; delinquent and violent behavior; and initiation into cigarette, alcohol, other drug use, or sexual activity. Repeated measures mixed model regressions found no effect of the intervention on rate of change in attitudes about drug use or frequency of delinquent or violent behavior. Regression analyses with multiple imputations for missing data detected group differences in means at 24-month follow-up. Both program formats reduced favorable attitudes toward drug use among youth (SA d = 0.39, PA d = 0.22); and AA youth in the self-administered intervention reported significantly less violent behavior than their control counterparts (d = 0.45). No effects were found for drug use harm or delinquency. Finally, logistic regression predicting a combined outcome measure of initiation of alcohol, tobacco, drug use, and/or sexual activity found AA youth in both the group- and self-administered intervention conditions significantly less likely to initiate substance use and/or sexual activity than those in the control condition. Odds ratios indicated the chances of initiating sex or substance use were reduced by almost 70% (OR = 0.31) for AA teens in the SA condition compared to controls, and 75% (OR = 0.25) for the AA teens in the PA compared to controls.