In this work, a comparison between fragility curves developed for regular and non regular reinforced frames is presented. The fragility curves are develop through the “Cloud Analysis“ procedure, which evaluates the structural response via Non-Linear Time History Analysis (NLTHA). Three 3D reinforced concrete multi-story frames characterized by different regularity are analyzed in this work. Both maximum inter-story drift and maximum chord rotation demand capacity ratio (calculated by the Italian Code) are used as Engeneering Demand Parametre thresholds. To complete the develop of the fragility functions, scalar intensity measures are selected among the most referred in practice and literature, both structure indepent and structure dependent. This work shows the influence of regularity in the damage levels of the buildings and the uncertainties given by the selection criteria for EDP threshold necessary for a correct representation of the Limit State.