Like many other non governmental organizations (NGOs) that provide assistance to vulnerable populations living in difficult and resource-limited settings, Médecins Sans Frontières (MSF) is confronted with situations for which proven, effective interventions are often lacking and/or where there is need for strong advocacy for improving medical care. As a result, MSF has become an important contributor to health research, and has dedicated resources to guide operational research by establishing its own Ethics Review Board, an innovation fund, an online publications repository and by regularly contributing to major scientific conferences. However, this increased research activity has led to concern that priorities and resources may be diverted away from the essential mandate of care provision for NGOs. In response, this article discusses the potential role operational research can play within medical NGOs such as MSF, and highlights the relevance of operational research, the essential elements of developing it within the organisation and some of the perceived barriers and solutions.