This case study demonstrates the importance of knowledge exchange in public health research. The study compares different approaches to knowledge exchange between five Centres of Excellence in Public Health Research. As six communications and knowledge exchange professionals working across different universities and public health organizations, we faced challenges in sharing and comparing our experiences. By applying a comparative case study methodology using a conceptual model, we were able to collectively reflect on our experiences and to distinguish between different dimensions in each case study that helped us to identify the advantages and disadvantages of each approach. Our comparison shows the benefits and challenges of working collaboratively with policy and practice partners in research and provides suggestions for linking a range of activities that engage policymakers at different levels, intensities, and points in their decision-making processes to build relationships (structural approach).