OBJECTIVES: A growing concern is that health policy and system researches (HPSR) should address the needs of potential users, and subsequently have substantial impacts on policy decisions and professional practices. The purpose of this study is to describe the experience on the annual HPSR topic prioritization conducted by Thailand’s Health Systems Research Institute and its alliances. METHODS: Narrative descriptive and quantitative approaches were employed to illustrate the processes of and results from the HPSR topic prioritization in 2010. RESULTS: The prioritization process was carried out on the basis of systematicness and transparency, with participation by key stakeholders including policymakers, academics, health professionals, civil society, and industries. There was a call for research topic proposals from stakeholders in November and December 2009. A total of 120 topics suggested by 66 organizations were then prioritized by 90 representatives of stakeholder organizations. Multiple criteria introduced in this step involved policy relevance; disease burden; economic impact; social and ethical aspects; variation in practices; possibility of changing practices; and public concerns. it was found that topics related to diseases with high burden, relating to service delivery especially on health promotion and disease prevention, and those submitted by central government agencies were more likely to get high priority than others. In addition, results from self-administrative survey demonstrated that over 92% of stakeholders strongly supported and expressed their interest to participate in the next annual topic prioritization process. CONCLUSIONS: This case study demonstrated that it is feasible to develop clear criteria and transparent process for prioritization of HPSR topics. Lessons learned from this case study can be useful for improving mechanism for selecting HPSR topics in other settings.