BackgroundRobust, flexible, and integrated health information (HIS) systems are essential to achieving national and international goals in health and development. Such systems are still uncommon in most low and middle income countries. This article describes a first-phase activity in Tanzania to integrate the country’s vertical health management information system with the help of an interoperability layer that enables cross-program data exchange.MethodsFrom 2014 to 2019, the Tanzanian government and partners implemented a five-step procedure based on the “Mind the GAPS” (governance, architecture, program management, and standards) framework and using both proprietary and open-source tools. In collaboration with multiple stakeholders, the team developed the system to address major data challenges via four fully documented “use case scenarios” addressing data exchange among hospitals, between services and the supply chain, across digital data systems, and within the supply chain reporting system. This work included developing the architecture for health system data exchange, putting a middleware interoperability layer in place to facilitate the exchange, and training to support use of the system and the data it generates.ResultsTanzania successfully completed the five-step procedure for all four use cases. Data exchange is currently enabled among 15 separate information systems, and has resulted in improved data availability and significant time savings. The government has adopted the health information exchange within the national strategy for health care information, and the system is being operated and managed by Tanzanian officials.ConclusionDeveloping an integrated HIS requires a significant time investment; but ultimately benefit both programs and patients. Tanzania’s experience may interest countries that are developing their HIS programs.