BackgroundThe Saudi Vision 2030 project recognized the integral role of health research in transforming, modernizing and governing the healthcare system, as well as improving health. The nature of health research prioritization is context-specific, and there is an obligation to effectively allocate resources to initiatives that will achieve the greatest impact, which is discussed in this paper.MethodsThe best practice for health research prioritization depends on the existing needs and context. The e-Delphi technique was conducted via an online self-administered questionnaire that covered health research topics, topics related to Vision 2030, as well as collaborative research. Criteria used for scoring the selected topics were: appropriateness, relevance, feasibility, urgency, collaboration and impact of research outcome. Research domains were prioritized by ranking the weighted mean aggregate score and all topics of the top five ranked domains, along with the aggregate scores of the answers of those in leadership positions were pooled together, validated, verified, summarized, refined and then classified into themes. ResultsThe participants included those from a full range of health specialties and subspecialties (46.5% physicians, 39% health specialists, 10% pharmacists and 3.6% dentists), and the study achieved balanced regional participation and covered a wide spectrum of qualification and professional levels. In total there were 2252 participants and 98% belonged to MoH. Of those from the MoH, 134 were leaders (85 Headquarters policy makers and 49 regional decision makers), while the rest were made up from individuals from 16 Health Affairs Directorates spanning 75 hospitals and specialized health centers, 24 primary health care centers , 2 healthcare clusters, in addition to five medical cities. Community involvement was represented by 26 organizations. Approximately half of stakeholders contributed to scientific research, while 24% had previous publications, and only 6% had a direct influence in health policymaking. The study deliverables were listed into three agendas:1. Health System Research Priority Themes: Service Delivery, Workforce, Information Systems, Access to Essential Medicines, Financing, Governance & Leadership and Disaster Response. 2. Diseases and Health Problems Themes: Non-Communicable and Communicable Diseases, Trauma, Public Health, Dental Health, Environmental Health, Pilgrims’ Health, Women’s Health, Child & Geriatric Health, Biomedical Technology, Radiology and Physical Technology.3. National and International Collaborative Research Themes: Major research areas impacted by COVID-19, Public Health, ‎ Healthcare Access, Medical Care & Universal Health Coverage, Value-based Healthcare, Health System Financing and Economics, Health Information and Communication Technology, Health System Governance, Health Workforce Development and Health System Preparedness and Response to Emergency.Conclusion Adequate description of the stakeholders and the methodology can strengthen legitimacy, credibility and maximize the impact of the priority setting process. Involvement of policymakers, researchers and funding organizations increases the opportunity of translation into actual research, supports redesigning the research landscape and ensures uptake of results and integration.