This collective case study examines secondary science teachers’ responses to a professional development program designed to assist in the transformation of inquiry belief structures and inquiry instructional practices. These teachers were participants in a year-long professional development institute that focused on increasing the quantity and quality of inquiry in secondary science classrooms. This multi-case design examines multiple data sources in order to answer the following research question: How do the beliefs and practices of teachers regarding inquiry-based instruction evolve over the year of intervention? Participants were selected using the data from an inquiry observational protocol to represent a variety of abilities and beliefs regarding inquiry instructional practice. The results provide insights into teachers’ belief structures and classroom structure related to inquiry instruction. Further, we detail the role of the professional development experience in facilitating transformation of classroom practice. Implications for how professional development programs are developed and led are provided.