This study contributes to the development and application of the seismic risk assessment in big cities. It has been structured into two parts. The first part details the model to evaluate the physical damage on residential buildings and their impact on the population and population-related aspects. The second part describes its application to Barcelona. The method, namely Vulnerability Index, defines five damage states; the action is expressed in terms of the macro-seismic intensity and the seismic quality of the buildings by means of a vulnerability index. In order to apply this method to Barcelona a deterministic and a probabilistic scenario are used. A powerful and versatile tool based on Geographic Information Systems (GIS) was created. Throughout the years, detailed information on the design of buildings has been obtained by collecting and completing the database of the dwellings of the city of Barcelona. The results obtained showed the peculiarities of individual buildings and were consistent with the historical evolution of the populated city and with the characteristics of soils, thus establishing the solidity of this method. The damage to the population is significant and its evaluation strongly depends on casualty models. In this sense, it is necessary to consider the specific numerical values as a prediction of the order of magnitude of the evaluated quantities. The obtained results and conclusions offer a great opportunity to guide the action and decision making in seismic risk prevention and mitigation in big cities.