<p>Site effects indicate modifications in amplitude, frequency content and duration of ground motion, depending on the geological and geotechnical conditions of a site subjected to a seismic event. For the definition of the seismic action on structures, the Italian Building Code employs a simplified approach to account for site effects, based on the definition of soil classes. In this work, the role of Seismic Microzonation (SM) studies to define design response spectra was investigated, considering an application to Eastern Sicily (Italy). In the framework of Level 3 Seismic Microzonation (SM3) studies, the Engineering-Geological Map (GT_Map) and the Seismically Homogeneous Microzones (SHMs) Map were produced based on the geological and geotechnical data obtained for the study area. The subsoil model was defined for each SHM and a set of seven accelerograms was selected from the Engineering Strong Motion database using the REXELweb tool. Ground response analyses were performed and synthetic parameters representative of the local seismic amplification were computed. The procedure for the regularization of the average response spectrum obtained from numerical analyses was described. The regularized average response spectrum was compared with the elastic response spectrum provided by the Italian Building Code for each SHM to explore the role of SM studies in defining design response spectra. Findings obtained in this study provide valuable information for engineers and planners in developing interventions for seismic risk mitigation.</p>