Knowledge produced through applied health research is often of a form not readily accessible to or actionable by policymakers and practitioners, which hinders its implementation. Our aim was to identify research activities that can support the production of knowledge tailored to inform policy and practice. To do this, we studied an operational research approach to improving the production of applied health research findings.A 2-year qualitative study was conducted of the operational research contribution to a multidisciplinary applied health research project that was successful in rapidly informing national policy. Semi-structured interviews (n = 20) were conducted with all members of the project's research team and advisory group (patient and health professional representatives and academics). These were augmented by participant (> 150 h) and non-participant (> 15 h) observations focusing on the process and experience of attempting to support knowledge production. Data were analysed thematically using QSR NVivo software.Operational research performed a knowledge mediation role shaped by a problem-focused approach and an intent to perform those tasks necessary to producing readily implementable knowledge but outwith the remit of other disciplinary strands of the project. Three characteristics of the role were found to support this: engaging and incorporating different perspectives to improve services by capturing a range of health professional and patient views alongside quantitative and qualitative research evidence; rendering data meaningful by creating and presenting evidence in forms that are accessible to and engage different audiences, enabling them to make sense of it for practical use; and maintaining perceived objectivity and rigour by establishing credibility, perceived neutrality and confidence in the robustness of the research in order to unite diverse professionals in thinking creatively about system-wide service improvement.Our study contributes useful empirical insights about knowledge mediation activities within multidisciplinary applied health research projects that support the generation of accessible, practice-relevant and actionable knowledge. Incorporating such activities, or a dedicated role, for mediating knowledge production within such projects could help to enhance the uptake of research findings into routine healthcare and warrants further consideration.