The nonlinear response of structures is usually evaluated by considering two accelerograms acting simultaneously along the orthogonal directions. In this study, the influence of the earthquake direction on the seismic response of building structures is examined. Three multi-story RC buildings, representing a very common structural typology in Italy, are used as case studies for the evaluation. They are, respectively, a rectangular plan shape, an L plan shape and a rectangular plan shape with courtyard buildings. Nonlinear static and dynamic analyses are performed by considering different seismic levels, characterized by peak ground acceleration on stiff soil equal to 0.35 g, 0.25 g and 0.15 g. Nonlinear dynamic analyses are carried out by considering twelve different earthquake directions, and rotating the direction of both the orthogonal components by 30° for each analysis (from 0° to 330°). The survey is carried out on the L plan shape structure. The results show that the angle of the seismic input motion significantly influences the response of RC structures; the critical seismic angle, i.e., the incidence angle that produces the maximum demand, provides an increase of up to 37% in terms of both roof displacements and plastic hinge rotations.