<p>Structures designed to withstand an earthquake of significant magnitude, aftershocks provide additional challenges in such cases. The aftershocks are not isolated incidents; they commonly occur after the major earthquake and cause additional seismic losses. The current study examines the impact of multiple earthquakes on the likelihood of structure collapse from a probabilistic perspective. In the present study, stiffness irregular four-storey Reinforced Concrete (RC) framed structure with fixed and isolated bases were examined and evaluated using recorded fourteen single and seven multiple earthquakes with distinct characteristics. The Incremental Dynamic Analysis (IDA) method is used to generate fragility curves for fixed base and base-isolated structures. An equation is proposed based on the deaggregated fragility curves to determine the seismic loss of the structures. The results emphasize the significance of multiple earthquakes. When multiple earthquakes are experienced by stiffness irregular structures with base isolation, the likelihood of collapse is significantly decreased. In seismically active areas with frequent multiple earthquakes, base-isolated structures are more effective and also reduce the post-earthquake repair cost and time.</p>