Human African Trypanosomiasis (HAT), commonly known as sleeping sickness, is closer than ever to being eliminated as a public health problem. The main narratives for the impressive drop in cases allude to drugs discovery and global financing and coordination. They raise questions about the relationship between well-funded international clinical research and much less well-endowed national disease control programmes. They need to be complemented with a solid understanding of how (and why) national programmes that do most of the frontline work are structured and operate. We analyse archives and in-depth interviews with key stakeholders and explore the role the national HAT programme played in the Democratic Republic of the Congo (DRC), a country that consistently accounts for over 60% of HAT cases worldwide. The programme grew strongly between 1996, when it was barely surviving, and 2016. Our political economy lens highlights how the leadership of the programme managed to carve itself substantial autonomy within the health system, forged new international alliances, and used clinical trials and international research to not only improve treatment and diagnosis but also to enhance its under-resourced disease control system. The DRC, a country often described as ‘fragile’, stands out as having an efficient national HAT programme that made full use of a window of opportunity that arose in the early 2000s when international researchers and donors responded to the ambition to simplify disease control and make HAT treatment more humane. We discuss the sustainability of both the vertical approach embodied in the DRC’s national HAT programme and its funding model at a time when the number of HAT cases is at an all-time low and better integration within the health system is urgent. Our study provides insights for collaborations between unevenly-resourced international research efforts and national health programmes.