While many innovative teaching strategies exist, integration into undergraduate science teaching has been frustratingly slow. This study aims to understand the low uptake of research-based instructional innovations by studying 21 successful implementations of the Student Centered Active Learning with Upside-down Pedagogies (SCALE-UP) instructional reform. SCALE-UP significantly restructures the classroom environment and pedagogy to promote highly active and interactive instruction. Although originally designed for university introductory physics courses, SCALE-UP has spread to many other disciplines at hundreds of departments around the world. This study reports findings from in-depth, open-ended interviews with 21 key contact people involved with successful secondary implementations of SCALE-UP throughout the United States. We defined successful implementations as those who restructured their pedagogy and classroom and sustained and/or spread the change. Interviews were coded to identify the most common enabling and challenging factors during reform implementation and compared to the theoretical framework of Kotter's 8-step Change Model. The most common enabling influences that emerged are documenting and leveraging evidence of local success, administrative support, interaction with outside SCALE-UP user(s), and funding. Many challenges are linked to the lack of these enabling factors including difficulty finding funding, space, and administrative and/or faculty support for reform. Our focus on successful secondary implementations meant that most interviewees were able to overcome challenges. Presentation of results is illuminated with case studies, quotes, and examples that can help secondary implementers with SCALE-UP reform efforts specifically. We also discuss the implications for policy makers, researchers, and the higher education community concerned with initiating structural change.