Although interactive technology is presumed to increase student understanding in large classes, no previous research studies have empirically explored the effects of Clicker Cases on students' performance. A Clicker Case is a story (e.g., a problem someone is facing) that uses clickers (student response systems) to engage students in understanding the meaning of the science contained within the story. Using an experimental randomized Solomon design across 11 institutions, we found that Clicker Cases increased student understanding more than PowerPoint lectures in large introductory biology classrooms, although there was variation across institutions and topics. By examining student performance in conjunction with faculty experience, we found that strong Clicker Cases created dissonance, captured attention and involved students in interpreting data or making decisions. This study provides a model for collaborative research across multiple institutions and demonstrates the need for using multiple institutions and topics in research on education.