Treatment evaluation for alcohol problem, runaway adolescents and their families is rare. This study recruited primary alcohol problem adolescents (N = 119) and their primary caretakers from two runaway shelters and assigned them to (a) home-based ecologically based family therapy (EBFT), (b) office-based functional family therapy (FFT), or (c) service as usual (SAU) through the shelter. Findings showed that both home-based EBFT and office-based FFT significantly reduced alcohol and drug use compared with SAU at 15-month postbaseline. Measures of family and adolescent functioning improved over time in all groups. However, significant differences among the home- and office-based interventions were found for treatment engagement and moderators of outcome.