Abstract: Aftershocks can cause additional damage to mainshock-damaged structures and threaten structural safety under earthquakes. In the light of this, this study extends the conventional seismic fragility theory and conducts the fragility analysis for a five-story RC frame structure designed according to the current Chinese design codes using the earthquake inputs of real and artificial mainshock-aftershock earthquake sequences. Based on the obtained fragility results for earthquake sequences, the limit state failure probabilities, damage state failure probabilities, and the vulnerability index corresponding to the earthquake sequences of different hazard levels are calculated for evaluating the structural safety under sequential earthquakes. The results show that the structural fragility due to mainshock-aftershock earthquake sequences is higher than that due to mainshock earthquakes alone. The artificial earthquake sequences may cause larger structural fragility than the real earthquake sequences. The artificial earthquake sequences based on the repeated method shows the largest damage potential for the structure among the used real and artificial earthquake sequences. The artificial earthquake sequences based on the attenuation method has a similar damage potential to real earthquake sequences.