Flat-slab RC buildings exhibit several advantages over conventional moment-resisting frames. However, the structural effectiveness of flat-slab construction is hindered by its alleged inferior performance under earthquake loading. Although flat-slab systems are widely used in earthquake prone regions of the world, fragility curves for this type of construction are not available in the literature. This study focuses on the derivation of such fragility curves using medium-rise flat-slab buildings with masonry infill walls. The study employed a set of earthquake records compatible with the design spectrum selected to represent the variability in ground motion. Inelastic response-history analysis was used to analyze the random sample of structures subjected to the suite of records scaled in terms of displacement spectral ordinates, whilst monitoring four performance limit states. The fragility curves developed from this study were compared with the fragility curves derived for moment-resisting RC frames. The study concluded that earthquake losses for flat-slab structures are in the same range as for moment-resisting frames. Differences, however, exist. The study also showed that the differences were justifiable in terms of structural response characteristics of the two structural forms.