The processes of regionalization and federalization are unquestionable trends in Europe considering the flow of powers from states to subnational levels. In multi-level systems, the patterns of regional and national careers reflect this structural evolution. In the literature, two positions oppose each other about the effects of regionalism. Some authors argue that it does affect career patterns while other scholars found little evidence of the regionalism hypothesis. Unclear results in the literature are partly due to the limited number of comparative research across countries and across time, bias in case selection, and the choice of the unit of analysis. Addressing these three issues, this article aims at testing the regionalism hypothesis based on an original dataset of 4.991 regional and national political careers in Belgium (Flanders, Wallonia, and Brussels), Canada (Ontario and Quebec), Spain (Catalonia and Castilla-La-Mancha), and the UK (Wales and Scotland). The intranational and international comparison of cases of strong and weak regionalism proves that regionalism does matter – regional politics attracts more professionalized MPs where regionalism is stronger – but the national parliament remains ultimately the most attractive political arena across regions.