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Setback in elevation of a structure is a special irregularity with considerable effect on its seismic performance. This paper addresses multistory Reinforced Concrete (RC) frame buildings, regular and irregular in elevation. Several multistory Reinforced Concrete Moment Resisting Frames (RCMRFs) with different types of setbacks, as well as the regular frames in elevation, are designed according to the provisions of the Iranian national building code and Iranian seismic code for the high ductility class. Inelastic dynamic time-history analysis is performed on all frames subjected to ten input motions. The assessment of the seismic performance is done based on both global and local criteria. Results show that when setback occurs in elevation, the requirements of the life safety level are not satisfied. It is also shown that the elements near the setback experience the maximum damage. Therefore it is necessary to strengthen these elements by appropriate method to satisfy the life safety level of the frames.