This publication examines the policy of Russia and the United States in the post-Soviet space in the first two decades of the 21st century. The materials were information sources on the foreign policy of the two countries, as well as research by Russian and Western authors using general scientific and special historical methods. The purpose of the article is to examine the role and place of the post-Soviet space in Russian-American relations in the 21st century. In the 21st century, the post-Soviet space has become an arena of geopolitical rivalry between Russia and the United States. This happened due to the cardinal divergence of the national interests of Moscow and Washington in the region. The United States decided to reformat the post-Soviet space, finally ousting the Russian Federation with the prospect of changing the political regime in Russia itself. The realization of this fact by the Kremlin has led to the strengthening, to the best of its ability, of Russian opposition to American penetration into the region. Consequently, in the 21st century, the post-Soviet space has become one of the irritants of Russian-American relations.