Background: Over the past decades active community engagement in health research has gained significant attention in people-centered health systems throughout the world. Yet there is little evidence about how best to enhance active community engagement in setting priorities for health research, particularly from low-and middle-income countries (LMICs). This study presents the approaches employed to identify health research priorities and the lesson learnt from the Northern Cape Province in South Africa. Methods: A combination of approaches involving the Essential National Health Research (ENHR), and the World Cafe consultation processes with the support of experts’ ideas used to enhance key stakeholders (n=41) participation towards the identification of health research priorities for the province. A document on the burden of diseases, health systems challenges and population health status indicators was presented and critically reviewed at the workshop. Results: The top ten health research prority areas for the province identified with active community engagement. More than 90% of the prioritised research areas are operational research which are linked to health services delivery challenges including health systems issues, burden of diseases, health program effectiveness, and the social determinants of health. Conclusion: Active community engagement in setting research priorities for health is a necessary first step to improve the delivery of good quality, equitable and accessible healthcare services for all citizens. However, the current limited resource capacities both in terms of funding and human resources for health research is a concern; and may hamper the effective translation of research priorities to actual action.