Global health governance represents an increasingly relevant yet largely understudied topic of international relations. The EU has established the capacity to play a leading role in health not only within the EU but also as an international actor at the World Health Organisation (WHO) – the “centre court of global health policy” (Jørgensen 2009) – as exemplified by the successful negotiations on the WHO Framework Convention on Tobacco Control. Still, limited and shared competences and the complex institutional configuration lead to a fragmented picture of the EU, impacting not only its negotiation performance but also the functioning of inter-organisational relations in health matters. The study will apply a rational institutionalist perspective, starting from an analysis of the structural changes brought by the Lisbon Treaty that affect the set-up for (external) public health policy. In a second step, the article investigates on patterns of interaction and discourses during the ongoing negotiations on the WHO Pandemic Influenza Preparedness Framework – a focus particularly promising in the light of the recently introduced Union competence to combat “cross-border threats to health” (Art. 152 TFEU). By analysing internal coordination and external representation processes between EU, Member States and WHO under both the Nice and the (unrolling) Lisbon set-up, the paper explores the question in how far the EU’s new institutional architecture enables the Union to live up to its ambition to contribute to (effective) multilateralism and inter-organisational cooperation.