Governments around the globe are paving the way for healthcare services that can have a profound impact on the overall well-being and development of their nations. However, government programs to implement health information technologies on a large-scale are challenging, especially in developing countries. In this article, the process and outcomes of the large-scale implementation of a hospital information system for the management of Brazilian university hospitals are analyzed. Based on a qualitative approach, this research involved 21 hospitals and comprised a documentary search, interviews with 24 hospital managers and two system user focus groups, and a questionnaire of 736 respondents. Generally, we observed that aspects relating to the wider context of system implementation (macro level), the managerial structure, cultural nuances, and political dynamics within each hospital (meso level), as well as the technology, work activities, and individuals themselves (micro level) acted as facilitators and/or obstacles to the implementation process. The dynamics and complex interactions established between these aspects had repercussions on the process, including the extended time necessary to implement the national program and the somewhat mixed outcomes obtained by hospitals in the national network. Mostly positive, these outcomes were linked to the eight emerging dimensions of practices and work processes; planning, control, and decision making; transparency and accountability; optimization in the use of resources; productivity of professionals; patient information security; safety and quality of care; and improvement in teaching and research. We argued here that to maximize the potential of information technology in healthcare on a large-scale, an integrative and cooperative vision is required, along with a high capacity for change management, considering the different regional, local, and institutional contexts.