This paper presents a parametric study on the inelastic response of six-story reinforced concrete (RC) frames subjected to mainshock-aftershock (MS-AS) ground motions. For this purpose, bare frame (BF), and four masonry RC frames with two infill thicknesses (75 or 125 mm) and two infill patterns (open ground story or fully infilled) are considered. They are situated at site class C in Vancouver, Canada, and are designed for office occupancy according to the 2005 National Building Code of Canada. The five frames are subjected to hundred ensembles of MS-AS ground motions scaled to seismic hazard level corresponding to the return period of 2500 years. For each sequence of earthquakes, change in the fundamental period (T 1 ) and inter-story drift (ISD) for both MS-AS sequences are quantified. The analysis results show that the period change and ISD were significant for BF, whereas the infilled frames sustained small damage with negligible change in T 1 .