Sometimes, one is forced to create large openings in the slab of an existing multistory building for various purposes for examples to construct additional stairs, lighting purpose, elevator and other architectural features. This study examined the seismic performance of multistory building with created large openings in the slabs .The main parameters, taken into considerations are: area, position of openings and number of stories. The effect of these variables on top displacement, story drift and story shear force was considered through a numerical study. Finite element analysis using ETABS 2015 program to predict the structural behavior where statically lateral loads were applied using traditional code method. The analysis was performed according to Egyptian building code. The grade of concrete was C300 and reinforcement 36/52 in all cases. The analysis was performed and the obtained results were evaluated and discussed to evaluate the effect of openings in the slabs of multistory building under seismic loads. Finally, some important conclusions declaring the effect of the created were given.