Starting from the Middle Ages up to today the South Caucasus has been witness to the competition and the rivalry that has developed between different great powers for control and influence in the region. This competition has been especially high after the three South Caucasian states, Armenia, Azerbaijan, and Georgia gained independence in 1990, and became caught up in the newly evolving power game between the Russian Federation, Republic of Turkey, the Islamic Republic of Iran, and the United States. The presence of the great powers in the region has left its traces on the regional developments, and the aim of this paper is to find out what role the great powers have had on the Nagorno-Karabakh conflict, the roots of which can be traced to the beginning of the 20th century. The study of the conflict through the prism of Offensive Realism has shown that the Nagorno-Karabakh conflict has become a tool in the hands of the great powers, which have used it to reach their ambition in the region, strengthen their position in the South Caucasus, and challenge there the presence of other great powers. For this purpose the great powers have intervened in the war, aided one of the conflicting sides, manipulated the mediations, all of which has resulted in a prolonged war-process, new series of violence and deadlocked meditations.