This report describes the OCB Khayelitsha Project, initiated in 2000, as one of the first MSF projects in Africa to introduce antiretroviral treatment (ART) into the public sector. Currently implementing HIV and tuberculosis (TB) programs, it has produced dozens of very well-received publications in peer-reviewed scientific journals, in large part because of its innovative strategies, major investment in a locally driven monitoring and evaluation system, and a long-standing collaboration with the University of Cape Town (UCT), civil society and local health authorities. Today most organizations and governmental bodies in South Africa perceive MSF as a catalyst for innovation and look forward to testing new approaches piloted by the organization. The evaluation urges MSF to maintain a balance between new pilots and a focus on the big picture to keep influencing the system as a whole. Other recommendations focus on optimising the learning provided by MSF's pioneering approaches in South Africa.