The introduction of open educational resources (OER) in two Ghanaian universities through a grant-funded project was embraced with a lot of enthusiasm. The project started on a high note and the Colleges of Health Sciences in the two universities produced a significant number of e-learning materials as health OER in the first year. Growing challenges such as faculty time commitments, technological and infrastructural constraints, shortage of technical expertise, lack of awareness beyond the early adopters and non-existent system for OER dissemination and use set in. These exposed the fact that institutional policy and integration was essential to ensure effective implementation and sustainability of OER efforts. Informed by the early OER experiences at the two institutions, this paper proposes that institutions in low resource settings perhaps need to pay close attention to awareness creation, initiative structuring, funding, capacity building, systemization for scalability and motivation if OER sustainability is to be achieved.