This paper illustrates an investigation on the effectiveness of the pushover procedures to evaluate the seismic response of three-dimensional, plan-asymmetric structures. In particular, both single-mode-based and multimodal-based horizontal force distributions were considered. The investigation concerns a set of eight-storey, single-bay spatial RC frames, characterized by different plan irregularities, expressed in terms of eccentricity between centre of mass and centre of stiffness and moment of inertia of the floor mass. Results of the pushover analyses have been compared with those of non-linear time history analyses, performed considering the structures subjected to a set of recorded ground motions scaled to the design seismic intensity. The response parameters considered in this study are floor displacements, rotations and inter-storey drifts referred to the centre of mass and displacements and inter-storey drifts of the frames lying in direction of seismic action.