This article presents a synthesis of five country studies of the sustainability of U.S. government-funded health projects in Central America and Africa. The studies reviewed health projects with a comparative framework to determine which project activities had continued after the donor funding ceased. This review found that health projects in Africa were less firmly sustained than those in Central America. The studies then evaluated context factors and project characteristics that were related to the sustainability of the projects. The weak economic and political context of the African cases was found to inhibit sustainability in those countries, suggesting that broader development issues be addressed before donors expect significant sustainability of health projects in Africa. Even in Central America it was found that the strength of the institution implementing the project was an important variable for sustainability, suggesting that donor attention also be shifted toward strengthening institutional development in order to assure sustainability. In addition to context factors, several project characteristics were related to sustainability in most cases and suggest sustainability guidelines for project design and implementation. The article concludes that projects should be designed and managed so as to: (1) demonstrate effectiveness in reaching clearly defined goals and objectives; (2) integrate their activities fully into established administrative structures; (3) gain significant levels of funding from national sources (budgetary and cost-recovery) during the life of the project; (4) negotiate project design with a mutually respectful process of give and take: and (5) include a strong training component.