Abstract: It has been reported that using single damage indicator is difficult to estimate the structural damage under earthquakes. In view of this, a framework of mainshock-aftershock fragility analysis method considering multiple damage indicators is developed in this study. In this framework, a stripe-based approach is used to simulate the accumulated damage under mainshock-aftershock sequences. The statistical failure probability is calculated by different damage indicators. The maximum values of statistical failure probabilities under each strip are taken as the representative failure probabilities. Integrated with the mainshock-aftershock intensities, the maximum likelihood function is generated, and the median value and logarithmic standard deviation of fragility function are obtained by solving the maximum likelihood function. Then the mainshock-aftershock fragilities considering multiple damage indexes can be obtained. The vulnerability index is used to evaluate the structural safety considering multiple damage indicators. To verify the method proposed in this paper, a RC frame structure designed with current Chinese seismic codes is taken as an example, and the maximum inter story drift and the Park-Ang damage index are selected as the two damage indicators. The fragility curve and the vulnerability index are calculated considering the two damage indicators. Comparing the results with those considering single damage indicator, it is found that the fragility curve and vulnerability index obtained by considering single damage index are different from those by considering two damage indexes. Therefore, it is suggested to consider multiple damage indexes in mainshock-aftershock fragility analysis. If only one damage parameter is considered, the maximum inter story drift should be selected when the mainshock-aftershock is weak, and the structural damage is light. When the earthquake intensity is high and the structural damage is severe, the Park-Ang damage index should be selected in the mainshock-aftershock fragility analysis.