Approximately one-quarter of all Canadian children will seek emergency care in any given year, with the two most common medical problems affecting children in the emergency department (ED) being acute respiratory illness and injury. Treatment for some medical conditions in the ED remains controversial due to a lack of strong supporting evidence. The purpose of this paper is to describe a multi-centre team grant in pediatric emergency medicine (PEM) that has been recently funded by the Canadian Institutes of Health Research (CIHR). This program of research integrates clinical research (in the areas of acute respiratory illness and injury) and knowledge translation (KT). This initiative includes seven distinct projects that address the objective to generate new evidence for clinical care and KT in the pediatric ED. Five of the seven research projects in this team grant make significant contributions to knowledge development in KT science, and these contributions are the focus of this paper. The research designs employed in this program include: cross-sectional surveys, randomized controlled trials (RCTs), quasi-experimental designs with interrupted time-series analysis and staggered implementation strategies, and qualitative designs. This team grant provides unique opportunities for making important KT methodological developments, with a particular focus on developing a better theoretical understanding of the causal mechanisms and effect modifiers of different KT interventions.