Russia and the United States, pursuing their national interests in the Middle East, were also involved in the Syrian conflict. As a result, in the second decade of the 21st century, Syria became one of the irritants in Russian-US relations. The protests that began in Syria in 2011 within the framework of “the Arab Spring” led to a serious political confrontation between Assad’s regime and the opposition with the participation of external geopolitical players. Pursuing their national interests in the Middle East Russia and the USA were also involved into the conflict, which made Syria one of the irritators in the Russian-US relations. The purpose of the article is to consider the impact of the Syrian conflict on the evolution of RussianUS relations. Employing general scientific and special historical methods the author uses the mass media materials and the documents published by the governmental and expert structures as well as publications of Russian and Western researchers to explore the impact that the Syrian conflict has on the Russian-US relations. The author analyses the reaction of the US and Russia to the events in Syria and shows their approaches to them. The USA supports the opponents of President B. Assad while the Russian Federation defends the interests of the official Damascus, which made them participants in the Syrian conflict. A conclusion is drawn that the opposing views of Moscow and Washington on the conflict in Syria remains an insurmountable obstacle to the diplomatic settlement of the Syrian issue. Even the common threat from ISIL has not made Russia and the US partners in the Middle East. The author explains this by the fact that the solution to the Syrian conflict has been held hostage to the tense Russian-US relations which have considerably deteriorated since the Ukrainian crisis.