This article presents the results of a mediation analysis of Project MYTRI (Mobilizing Youth for Tobacco Related Initiatives in India), a randomized, controlled trial of a multiple-component, school-based tobacco prevention program for sixth- to ninth-graders (n = 14,085) in Delhi and Chennai, India. A mediation analysis identifies how an intervention achieves its effects. In MYTRI, changes in students’ (a) knowledge about the negative health effects of tobacco, (b) beliefs about its social consequences, (c) reasons to use tobacco, (d) reasons not to use tobacco, (e) advocacy skills self-efficacy, and (f) normative beliefs about tobacco use were significantly associated with reductions in students’ intentions to use tobacco and tobacco use behaviors. In contrast, changes in students’ perceptions of the prevalence of smoking and chewing tobacco were significantly related to increases, in students’ intentions to use and use of tobacco. Implications for intervention design are considered.