BackgroundHealth research is conducted with the expectation that it advances knowledge and eventually translates into improved health systems and population health. However, research findings are often caught in the know-do gap: they are not acted upon in a timely way or not applied at all. Integrated knowledge translation (IKT) is advanced as a way to increase the relevance, applicability and impact of research. With IKT, knowledge users work with researchers throughout the research process, starting with identification of the research question. Knowledge users represent those who would be able to use research results to inform their decisions (e.g. clinicians, managers, policy makers, patients/families and others). Stakeholders are increasingly interested in the idea that IKT generates greater and faster societal impact. Stakeholders are all those who are interested in the use of research results but may not necessarily use them for their own decision-making (e.g. governments, funders, researchers, health system managers and policy makers, patients and clinicians). Although IKT is broadly accepted, the actual research supporting it is limited and there is uncertainty about how best to conduct and support IKT. This paper presents a protocol for a programme of research testing the assumption that engaging the users of research in phases of its production leads to (a) greater appreciation of and capacity to use research; (b) the production of more relevant, useful and applicable research that results in greater impact; and (c) conditions under which it is more likely that research results will influence policy, managerial and clinical decision-making.MethodsThe research programme will adopt an interdisciplinary, international, cross-sector approach, using multiple and mixed methods to reflect the complex and social nature of research partnerships. We will use ongoing and future natural IKT experiments as multiple cases to study IKT in depth, and we will take advantage of the team’s existing relationships with provincial, national and international organizations. Case studies will be retrospective and prospective, and the 7-year grant period will enable longitudinal studies. The initiation of partnerships, funding processes, the research lifecycle and then outcomes/impacts post project will be studied in real time. These living laboratories will also allow testing of strategies to improve the efficiency and effectiveness of the IKT approach.DiscussionThis is the first interdisciplinary, systematic and programmatic research study on IKT. The research will provide scientific evidence on how to reliably and validly measure collaborative research partnerships and their impacts. The proposed research will build the science base for IKT, assess its relationship with research use and identify best practices and appropriate conditions for conducting IKT to achieve the greatest impact. It will also train and mentor the next generation of IKT researchers.