The effect of foundation flexibility is generally ignored in seismic design of building structures. The design is commonly carried out on the results of static/dynamic analysis considering fixed-base condition. But for building frames are embedded on soft soil, this assumption is not reasonable and seismic responses resulting idealized model are not identical with responses of realistic model. The main objective of this research is to evaluate the effect of foundation flexibility on ductility demand of reinforced concrete frame structures. To achieve this goal a set of generic frame models with 5 story, 10 story and 20 story height are used to evaluate seismic responses of R/C frame buildings. The generic models are idealized as 3D frames using beam and column elements. The nonlinear behavior of beam elements is modeled by means of moment-curvature theory. Also in column elements, multi-axial spring model based on material stress-strain relation, called “fiber model”, is used to represent the interaction among tension/compression axial force and biaxial bending. The effect of foundation flexibility is considered by substructure method implementing the concept of impedance functions of foundation. So spring-damper supports are used to represent soil dynamic stiffness. The story ductility demand is determined as the ratio of ultimate inter-story drift to yielding inter-story drift. Nonlinear time history analysis (NTH) is carried out to evaluate ultimate inter-story drift. To achieve this goal, the foundation-structure system is subjected to a set of ground motions. The set consists of “ordinary” and “near fault” ground motions. Moreover, nonlinear static pushover analysis () is carried out to achieve yielding inter-story drift. The load pattern is defined by lateral forces back-calculated by response spectrum analysis (RSA) of the structure, assumed to be linearly elastic. The results indicate that soil-structure interaction mostly increases the ductility demand of these types of structures. Consequently, it is necessary to consider foundation flexibility effects in structural design of such building frames. Also results demonstrate that story ductility demand distribution over the height of the structure, significantly differs among the various generic models and maximum ductility demand occurs in different stories. Comparison among 1D excitation and 2D excitation of the generic models indicates that storey ductility demand of the structure increases in generic models with 2D excitation. This increment considerably depends on natural period, lateral strength of the structure and frequency content of the near fault ground motions.