Background: Health research can play a critical role in strengthening health systems.However, little monitoring of health research is conducted in African countries to identify whether research contributes to addressing local health priorities.Aim/Setting: To review the profile of research on the health service platform in the Western Cape province of South Africa which was approved by the health authorities over the period January 2011 to December 2012.Methods: Databases held by both the Provincial and City of Cape Town health departments were reviewed. Descriptions of research institution, location of research, topic and funding size and source were analysed.Results: Of the health research approved in the province, 56% of projects were located on the District Health Services platform and 70% were based in the Cape Metropolitan area. For projects reporting budgetary information, the total funding was US $29.2 million. The primary focus of research was on HIV and tuberculosis (TB), whilst relatively few studies addressed nutrition, mental health or injury and there was little health systems research. Research funding was dominated by very large grants from foreign funders for HIV and/or TB research. South African government sources comprised less than 8% of all health research funding.Conclusion: There is a partial mismatch of donor funding to local health priorities. Greater focus on neglected areas such as mental health, trauma, nutrition and non-communicable disease, as well as greater investment in health systems research, is needed. Unless governments increase funding for research and a culture of research translation is achieved, health research will have limited impact on both local and national priorities.