INTRODUCTION: Learning health systems (LHS) are an approach to translate patient data into actionable clinical insights, empower healthcare teams to drive quality improvement and reduce health inequalities. Here we present a protocol for a realist evaluation to explore what works to implement a learning health system approach in primary care settings in Thailand, for whom does it work, how, why and in what circumstances. METHODS AND ANALYSIS: A mixed-methods realist evaluation will run in parallel with an interventional trial [Reg No: NCT06873243] in Northern Thailand which aims to improve the management of hypertension (HTN), type 2 diabetes mellitus (T2DM) and chronic kidney diseases (CKDs) using a data-supported learning health systems approach. As part of the trial, 16 primary care units (PCUs) in Chiang Mai and Lamphun provinces will be randomly selected to receive a learning health system intervention to support quality improvement for care of HTN, T2DM and CKD. Performance will be compared between intervention PCUs and all other PCUs in the region. Participants of the realist evaluation will include clinical and other professional staff involved in the development and implementation of the LHS. This realist evaluation will use both quantitative and qualitative data, including semi-structured interviews, surveys and documents from participating sites. Quantitative and qualitative findings will be systematically integrated to test, refine and validate context-mechanism-outcomes to identify consistencies, contradictions and explanatory mechanisms as part of a final programme theory for the successful implementation of the LHS. ETHICS AND DISSEMINATION: Ethical approval has been granted by all collaborating university Research Ethics Committees (ref: 1090, 0321, 32540). Results will be disseminated to stakeholders, including patients and the public, health providers, the Thai government and WHO office. Our methods and dissemination will be guided by National Institute for Health Research and Guidelines International Network reporting standards for Patient and Public Involvement and Engagement.