The proliferation of international and regional organisations in the last decades led to increasing overlap of memberships and mandates in social policy areas. Whereas the literature has explored the benefits and perils of institutional overlap though neglecting the social policy dimension of such processes, studies on regionalism have focused on single cases of regional organisations. This paper breaks new ground by examining the effects of the overlap in membership, health mandates and institutional mechanisms between the Common Market of the South (MERCOSUR) and the Union of South American Nations (UNASUR) between 2008 and 2018. It focuses on two cases of access to medicines: the creation of the medicine price bank and the price negotiation of high-cost medicines. Our argument is that the overlap was positive, leading to an incipient trend towards cooperation. This was facilitated by the membership structure, the expertise already accumulated in the region and the relations and networks among those involved in health regional cooperation. Overall, the article deepens our understanding of the conditions under which regional organisations, even in the context of institutional overlap, can contribute to adequately respond to transnational challenges, which, as global health, are not only persistent, but also profoundly affect our societies.