Background: Currently, the South African public healthcare system is hampered by a lack of effective patient data management. This leads to, amongst other challenges, a lack of transparency in the management of patients’ health information and unsecure medical records. Blockchain, on the other hand, can make healthcare records more secure, easily auditable, and hence more reliable. These advantages, among others, make Blockchain an appealing technology for managing patients’ health information in the South African context.Objectives: The study investigated the antecedents of the adoption of blockchain technology as a tool to improve the management of patients’ health information in the South African public healthcare sector.Method: The four pillars of a health information system (strong leadership, contingency plan, security and privacy, and IT or vendor support) were adopted as the theoretical grounding for the study. Qualitative data were collected through interviews with IT specialists and healthcare professionals working in the public healthcare sector.Results: The study identified 11 antecedents that can be related to the four pillars of a health information system. These antecedents must be addressed for blockchain to contribute meaningfully to enhancing patients’ health information management in South Africa.Conclusion: Although blockchain can contribute meaningfully to addressing health information management challenges in South Africa, contextual factors need to be considered for it to fulfil its promises. It is anticipated that the study findings will help stakeholders in the South African public healthcare sector to make informed decisions in their quest to deploy technology innovations like blockchain.