Health information systems are central to strong health systems. They assist with patient and program management, quality improvement, disease surveillance, and strategic use of information. Many donors have worked to improve health information systems, particularly by supporting the introduction of electronic health information systems (EHIS), which are considered more responsive and more efficient than older, paper-based systems. As many donor-driven programs are increasing their focus on country ownership, sustainability of these investments is a key concern. This analysis explores the potential sustainability of EHIS investments in Malawi, Zambia and Zimbabwe, originally supported by the United States President’s Emergency Plan for AIDS Relief (PEPFAR).