In multilevel systems, patterns of regional and national political careers reflect processes of regionalisation and federalisation. Yet the effects of regionalism on the orientation of legislative careers remain disputed. Such disputes result from the choice of the unit of analysis, the scarcity of comparative research across countries and over time, and bias in case selection. This article offers a systematic intranational comparative analysis of ‘sister regions’ in four countries that are examples of weak and strong regionalism. It tests the regionalism hypothesis based on an original comparative dataset of 4662 regional and national political careers in Belgium, Canada, Spain, and the UK. The results demonstrate that regionalism matters: regional legislative elites emerge more clearly in polities in which regionalism is stronger. The regionalism hypothesis is particularly supported in Spain and Canada, which have a longer history of regional institutions, but that trend is also confirmed in the UK and Belgium.