Abstract Central western Argentina is identified as the most hazardous seismic zone in the country. Historical earthquakes with magnitudes greater than M s >6.0 frequently occur in this territory and are associated with the subduction of the Nazca plate. However, seismic hazards have not been fully assessed in this region. No secondary seismic effects of a potential earthquake with destructive consequences have been considered, nor has the existence of shallow Quaternary blind faults been identified by seismic surveys. Neotectonic studies performed up to the present describe only those Quaternary faults with some surficial expression. Lacking proper hazard assessment limits strategies to reduce the economic impact of drastic seismic events. This chapter is focused on the impact of major destructive earthquakes that have occurred in central western Argentina in order to understand the incidence of these phenomena in the past and to consider the vulnerability of the region in light of its increased urbanization and changing agricultural practices.