This paper employs the fragility function method to study the effects of dynamic fluid-structure interaction on seismic response of multi-span deep water bridges. Currently, two approaches are widely used to study the dynamic fluid-structure interaction effect of structures: the analytical ‘added mass’ method and full-scale two- or three dimensional finite element modeling. This paper offers a computationally economical yet adequate procedure. In this procedure, Morrison equation is employed to calculate the added mass for piles and columns, and a water-foundation coupling system is modeled to calculate the added mass for pile cap. In this water-foundation coupling system, a pile beam-element was adopted to avoid the thorough water domain modeling. A typical multi-span continuous composite girder bridge in China lying in deep water environment is used as a case study. The uncertainty of modeling parameters is considered using an experimental design method. The limit state functions are derived through a simple fuzzy model. Fragility functions of pier column and pile foundation are developed using nonlinear time history analysis. Fragility curves conditioned on different parameters in fuzzy models and different water depth are then compared to illustrate the effects of fuzziness and seismic hydrodynamic pressure. In general, for bridges with only pile surrounding water, the influence of water on potential damage of bridges is small and can be practically negligible. However, for the cases which the pile cap is under the water, increasing the water depth can generally increase the damage probability. It is concluded that for deep water bridges, the influence of dynamic fluid-structure interaction can be harmful to bridge responses, which aggravates with water depth by increasing the displacement of pile cap and introducing larger seismic demands on pier columns.