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The study reveals how the role of the largest cities – regional capitals in the urban settlement system – and the economy of the country changed during the period of social and economic transformations at the turn of the twentieth and twenty-first centuries. The object of the study is the largest cities with a population of over 1 million people, the administrative centers of the regions. Unlike Moscow and St. Petersburg, these are administrative centers or “capitals” of large territories that have the status of a constituent entity of the Russian Federation. The authors emphasize the special role of cities – regional capitals in post-socialist and developing countries – where there are significant and rapid changes in the distribution of functions between the center and the regions. At the same time, cities – regional capitals – are not considered as isolated objects, but as elements of a national settlement system, the leaders among Russian second-tier cities. The common features of the evolution of the largest regional capitals, the continuity of the factors of city formation, are revealed. Considerable attention is paid to assessing the consequences of the collapse of the Soviet Union for the development of the urban settlement system. It was concluded that the “compensatory” nature of the accelerated growth of the largest regional capitals in post-Soviet Russia. “Compensatory” growth is considered as a form of adaptation of the urban settlement system to the weakening of links between its essential links. A methodical approach is proposed that allows a comparative analysis of the role of the largest regional capitals and the capital of the state in the economy of the country. In the process of testing it, an assessment was made of population dynamics, as well as key economic indicators, such as the volume of products shipped, retail turnover, investments, the volume of work in the construction of major regional pages, as well as Moscow and St. Petersburg. The evaluation results allowed the classification of the largest regional capitals in terms of their role in the economic development of the country, as well as in terms of the extent of the gap between the indicators; on the one hand, the largest regional capitals, and on the other, Moscow and St. Petersburg.