Background <p>Living evidence syntheses (LES) provide decision-makers with continuously updated, systematically appraised research summaries to inform policy and practice decisions. However, little is known about how to enable effective use of LES in health policy decisions. This study aimed to understand and describe mechanisms that enable the use of LES to inform health policy decisions.</p> Methods <p>This study used semi-structured, in-depth interviews, followed by roundtables with policy-makers, knowledge intermediaries and researchers, internationally. Interviews explored participants’ experiences, challenges and opportunities regarding the use of LES in health policy. Roundtables were held to validate the interview findings and identify potential strategies to enable LES use. Qualitative data were analysed in three steps: First, outcomes representing LES use in health policy were defined using Proctor’s Implementation Outcomes Framework. Next, barriers and facilitators influencing these outcomes, and strategies to achieve the outcomes, were grouped using inductive thematic analysis. Finally, mechanisms explaining how the strategies could enable LES use in policy-making were described.</p> Results <p>A total of 22 participants from all geographic regions participated in the study. Aligning with Proctor’s Implementation Outcomes Framework, trust, relevance and communication between policy-makers and LES producers influenced acceptability and appropriateness; limited resources, data and technical capacity constrained feasibility; political will, clarity about uncertainty in evidence and the ability to adapt LES findings to local contexts influenced adoption and fidelity; and finally, ongoing institutional support, relevant and trustworthy LES outputs and stable relationships influenced cost, penetration and sustainability. Mechanisms to enable LES use included understanding the needs of LES users; increasing equitable access to useful LES; increasing reliable access to LES; enhancing capacity to use available LES; enabling health systems to implement policy decisions informed by LES; and building confidence in determining when and how to use LES.</p> Conclusions <p>Users and producers of LES from global policy contexts identified key influences on LES use in health policy and proposed strategies to enable its use. A systematic assessment of these strategies is necessary to determine their effectiveness across health policy contexts and enable equitable use of LES in health policy decisions.</p>