Background: The objectives of this article are to describe the process followed in development of the Swaziland’s national health research agenda (NHRA); and to provide an overview of the health research priorities that emerged from that process. Discussion: Swaziland followed a fourteen step process to develop it’s NHRA, namely: search and review of the existing health research priority setting guidelines; situation analysis included review of Swaziland’s socio-economic indicators; identification of research stakeholders; identification of the preliminary main broad research themes; development of questionnaire on ranking of main research themes; workshops with each of the eight stakeholders; ranking of major health themes and identification of sub-themes; identification of research gaps under each sub-theme and main research areas; scoring of research areas; research areas were grouped by sub-themes and ranked; collating research areas ranked as number one in each sub-theme; providing content to the agenda; preparation of the zero NHRA draft report; preparation of the first NHRA draft report taking into account critical inputs from stakeholders; and stakeholder’s final validation of the NHRA draft report. The paper provides an overview of communicable diseases, non-communicable diseases, sexual and reproductive health, injuries and health system research gaps under four categories of research: situation (burden and determinants); improvement of existing interventions; effectiveness of interventions; and feasibility of developing new capacities (tools and products). Conclusion: The National Health Research Department, with the support of the National Health Research Review Board, will be responsible for dissemination, preparation of rolling annual action plans to secure government funds for implementation of NHRA, promoting adherence among stakeholders, establishing a registry of R4H, establishing a knowledge translation platform, building of public-private-partnerships for research, mobilization of external resources, coordination and monitoring of the implementation of the NHRA. Keywords Swaziland, National Health Research Agenda, Health Research Priorities, Research Stakeholders, Research Gaps