Questions remain regarding whether professional development focused on response to intervention can be implemented effectively on a large scale. One important goal of professional development involves educators' beliefs regarding foundational response-to-intervention concepts (e.g., data-based decision making, importance of effective instruction). This study examined the relations between professional development focused on response to intervention and educators' beliefs. Participants (N = 3,961) were from 34 pilot and 27 comparison schools in a southeastern state. School leadership teams responsible for facilitating response-to-intervention implementation at pilot schools participated in 13 full-day trainings across 3 years. In addition, coaching support was provided to all pilot school educators including leadership team members. Multilevel modeling indicated that school leadership team membership predicted positive changes in beliefs regarding data-based decision making when compared with the remaining pilot and comparison school staff (p = 0.08; SE = 0.01; t[7,562] = 5.87, p < 0.0001). Pilot school membership predicted negative changes in beliefs regarding functions of core (Tier I) and supplemental (Tier II) instruction when compared to comparison school staff (ß = -0.05; SE = 0.02; t[7,565] = -3.13, p < 0.01). Implications for research and for practitioners challenged with facilitating response-to-intervention implementation as a large-scale systems change are discussed.