OBJECTIVE:In the context of growing financial pressures on health budgets, cost-effective prevention strategies are needed to address the burden from non-communicable disease in Australia. We explored how decision makers use economic evidence to inform such investment and how such evidence generated can more effectively meet the needs of end users. METHODS:Thematic analysis of in-depth interviews with 15 high level stakeholders (Treasury, state health departments and the insurance industry), supplemented by documentary analysis. RESULTS:Types of prevention approaches and economic evidence relevant to decision makers differed by organisational perspective. Capacity building in understanding economic evaluations and research evidence that addresses the differing criteria for investment used by different organisations is needed. The task of determining investment priorities in disease prevention comes with significant challenges including ideological barriers, delayed outcome measures, and implementation uncertainties. Conclusions and Implications for public health: Promoting the greater use of economic evidence in prevention requires more work on two fronts: tailoring the methods used by economists to better match the organisational imperatives of end users; and promoting greater consideration of broader societal and health sector perspectives among end users. This will require significant infrastructure development, monitoring and evaluation, stronger national leadership and a greater emphasis on evidence coproduction.