The piers of girder bridges have a very important role on the safety of the structural system to earthquakes. This paper addresses the seismic fragility of double-column (DC) bridge piers by focusing on the influence of the straining beams and the direction of seismic waves. The seismic capacity of eight DC piers with different number and position of straining beams is first studied by pushover analyses. These results are used to derive empirical formulas for the seismic capacity of general DC piers and to define damage indices for prescriptive damage states. Finite element models of typical girder bridges with the different piers are carried out next to assess the seismic demand of these piers and to generate fragility curves by comparing their seismic demand and damage indices at the defined damage states. Results indicate that: (1) DC piers are more vulnerable when subjected to longitudinal ground motions compared with the case of transverse inputs; (2) the damage probability of the piers for transverse seismic inputs decreases with the increasing relative height of the straining beams; and (3) DC piers with two straining beams have enhanced performance in the transverse direction compared with those with a single straining beam.