Since the last decade, the development of European Party Federations (EPFs) has been followed with increasing attention from scholars. However, the analysis of EPFs' impacts on EU policy-making has been quasi-neglected. Therefore, the main objective of the paper is to present a comprehensive conceptual framework for analysing the party interaction within EPFs and their effects on the EU policy-making. Accordingly, the argument will be developed in four steps. First, the paper will review the state of the art in order to show that a causal theory is missing. Secondly, it will ask how to construct a causal theory and how the analytical framework may be empirically tested. Thus, and thirdly, it will make clear that it approaches the EU as a useful location of policy-making. Fourthly, the paper will argue that it is necessary, on the one side, to focus on party interaction within EPFs and, on the other side, to distinguish between the decentralised and the centralised party interactions in order to adequately analyse the various effects of EPFs on the EU institutional modes. In this regard, the paper will not only elaborate the main descriptive and explanatory hypotheses but also illustrate most of them with empirical examples.