This article provides a detailed study of how bureaucratic politics in the European Commission can systematically affect the substance of the legislative agenda that makes up European integration. Based on an encompassing description of the bureaucratic policy-formulation process within the Commission, it shows how the Commission’s different elements play off against each other and thereby systematically advantage the lead department and the Secretariat-General. Empirical case studies from a sample of 48 policy formulation processes in the Commission during 1999–2008 illustrate how these structural advantages actually change the political substance of policy proposals. Against additional evidence on an uneven distribution of procedural advantages across the Commission departments, it concludes that bureaucratic politics in the Commission may account for systematic biases on the European Union’s legislative agenda.