In most current seismic investigations on bridges with tall piers, only mainshock actions are considered without incorporating the effect of mainshock-aftershock (MA) sequences. This paper investigates the seismic fragility and the associated direct financial losses of tall pier bridges subjected to MA sequences using the vector-based intensity measure considering both main- and after-shocks. Numerical model of a typical RC tall pier bridge is developed and validated through shake table test results. Nonlinear time-history analyses are extensively conducted to obtain the seismic responses of the bridge under MA sequences, which are further utilized for the development of fragility surfaces. The analytical results show that in the MA sequences, the contribution of the aftershocks to the peak structural seismic demands is basically negligible unless their intensities exceeding critical values. While the structural vulnerabilities increase with both the intensities of main- and after-shocks, the role of mainshocks is observed more substantial. On the other hand, however, by totally neglecting the effect of the aftershocks, the failure probability and financial loss of the tall bridge would be underestimated, particularly when strong aftershocks occur following mainshocks.