We conducted a group randomized trial of an interactive, games-based, tobacco cessation program (ACTION) designed to help adolescents who live in tobacco-growing communities to stop using tobacco. More than 260 high school students participated in this study, in 14 schools across three states. We collected self-reported measures of cigarette and smokeless tobacco use and conducted biochemical validation of self-reported use at three time points (pre-test, immediate post-test, and 90-day follow-up). We used multi-level modeling to account for intraclass clustering at the school and classroom levels, and we analyzed our results using an intent-to-treat approach and a per protocol approach. Using the per protocol analytic approach, ACTION participants were more likely than comparison participants to achieve abstinence at 90-day follow-up. We found no program effects on our secondary outcomes or mediating factors. This study suggests that ACTION has promise as a relatively effective adolescent cessation program, although the overall limited effectiveness of cessation programs for adolescents must be acknowledged.