While in poorly-detailed masonry-infilled reinforced concrete (RC) buildings the significance of masonry infills is acknowledged, less attention has been paid to the variability surrounding their mechanical properties and its potential impact on fragility and, consequently, vulnerability models to be used in seismic risk estimation. This study addresses this gap by proposing updated fragility and vulnerability models of existing poorly-detailed masonry infilled and pilotis RC frames that consider the variability in building layout and infill properties. A large building portfolio, representative of those designed according to Italian codes between 1970 and 1980, is selected as case study, incorporating building-to-building variability through various geometrical configurations. Updated modelling uncertainty parameters, specifically derived for existing infilled RC frames, are used, including the variability surrounding the properties of different infill typologies and the occurrence of RC frame shear failure. The portfolio was analysed through multiple-stripe analyses, followed by the development of upgraded fragility models for buildings with different heights and geometrical configurations. Finally, the corresponding vulnerability models were derived using damage-to-loss models calibrated with post-earthquake observation damage data from the 2009 L'Aquila earthquake. The updated fragility and vulnerability curves can be used for more refined seismic risk estimates of large building portfolios, that account for building-to-building and infill-to-infill variability, revised modelling uncertainty estimates and a more robust intensity measure (AvgSa).