Political fragmentation and resulting continuous warfare were important parts of European history, and it has been linked to innovation, economic growth, regime change, and state formation. Scholars have long debated the importance of the decade-long interregnum in the Roman Empire of the German Nation for this development. This article documents that the death of Emperor Frederick II in 1250 and the ensuing demise of the Hohenstaufen dynasty marked a divergence in central European history. Prior to 1250, the level of political fragmentation was similar in the Empire and other European states; after 1250, imperial areas saw a marked increase in local political autonomy compared to other areas. This difference in political fragmentation persisted until the modern period.