The Direct Displacement-Based seismic Design (DDBD) method has been a major development in the context of Performance-Based seismic Design of reinforced concrete (RC) frames. The method has been positively received from the engineering community, while, at the same time, significant improvements have been proposed. Even though its field of application is constantly widening, no specific rules are generally provided for specific cases, such as RC frames with setback irregularity, under the claim that, in this case, no modifications in the basic approach are needed. The validity of this assumption is examined by assessing the DDBD provisions through design of such irregular RC structures and assessment of their seismic performance under nonlinear static and dynamic analyses. Local ductility associated with global behavior is examined and incompatibilities in demands with the global design displacement are identified, where they occur. Guidelines are provided to ensure that rational performance results are obtained, when the DDBD method is applied.