In a seismically active region, structures may be subjected to multiple earthquakes, due to mainshock–aftershock phenomena or other sequences, leaving no time for repair or retrofit between the events. This study quantifies the aftershock vulnerability of four modern ductile reinforced concrete (RC) framed buildings in California by conducting incremental dynamic analysis of nonlinear MDOF analytical models. Based on the nonlinear dynamic analysis results, collapse and damage fragility curves are generated for intact and damaged buildings. If the building is not severely damaged in the mainshock, its collapse capacity is unaffected in the aftershock. However, if the building is extensively damaged in the mainshock, there is a significant reduction in its collapse capacity in the aftershock. For example, if an RC frame experiences 4% or more interstory drift in the mainshock, the median capacity to resist aftershock shaking is reduced by about 40%. The study also evaluates the effectiveness of different measures of physical damage observed in the mainshock-damaged buildings for predicting the reduction in collapse capacity of the damaged building in subsequent aftershocks. These physical damage indicators for the building are chosen such that they quantify the qualitative red tagging (unsafe for occupation) criteria employed in post-earthquake evaluation of RC frames. The results indicated that damage indicators related to the drift experienced by the damaged building best predicted the reduced aftershock collapse capacities for these ductile structures.