During the first weeks of the Covid-19 pandemic, European Union (EU) member states competed over scarce countermeasures. Regarding vaccines, a few member states launched exclusive joint endeavours, yet eventually, the EU centralised vaccine provisioning. The EU’s external vaccine diplomacy proceeded almost inversely. After stepping into the breach in global health governance, European leadership faltered and global collaboration progressed more slowly. This article explores Europe’s diverging trajectories in the regional and global provisioning of Covid-19 vaccines. Focussing on the European Commission’s leadership, we investigate to what extent it promoted regional and international cooperation and with what success. We also explain which factors enabled and constrained Commission leadership. Employing a controlled comparison and process tracing, we find that Commission leadership was more extensive and impactful in regional than in global vaccine provisioning. Member state support was the main enabling condition. Without support, institutional capacity and resources were insufficient for impactful leadership.