Masonry buildings present plan or vertical irregularity generally caused by structural modifications suffered over time. Most recent earthquakes highlighted how structural irregularity strongly affects the vulnerability and the seismic response of masonry buildings. In the context of historical city centres, vertical irregularity due to sudden variations in mass, stiffness and strength on walls along the building height, was investigated. In the center of Florence the vertical irregularity is often due to changes made over time for functional needs or for an economic return. Large portions of masonry walls on the ground floor were removed to allow a new distribution of the interior spaces and the scheme of the openings at the different floors of the building due to the internal renovation of the flats, the partial rooftop addition, usually for an economical return, as common in densely populated urban areas. In this paper, a simplified numerical procedure is proposed to evaluate the influence of vertical irregularity on the seismic response of masonry walls along the building height. This simplified procedure can be useful for both academic research and professional activity.