Santa Maria Paganica Church, built in the second half of XIII century, represents one of the most important church for L’Aquila history (being the second so-called “capoquarto” church). During the centuries, due also to the damages suffered by various earthquakes, important structural modifications, which are decisive for the interpretation of the seismic response, followed. In particular, as a consequence of L’Aquila earthquake (April 6, 2009), severe collapses interested the church, which in particular occurred in: the dome and dome cladding, the whole roof (with exception of apse), the upper part of the lateral wall on left side, the gable of façade. Several vulnerability factors facilitated the collapse of these portions, in particular: the constructive precariousness of nave’s masonry walls; the asymmetric transversal stiffness on the two opposite sides of nave; the replacement of the original roof. In the paper, starting from the analysis of the constructive details and the subsequent transformations which interested this church, the interpretation of its seismic response will be discussed. Moreover some preliminar issues, associated to the different solutions for the church rebuilding and the strengthening interventions which should be adopted, will be examined.