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Earthquake-induced pounding in bridges is a complex contact phenomenon in which the dynamic responses of structures, including collisions between deck and abutments, are strongly related to structural properties and earthquake excitation. The goal of this study is to develop and compare the seismic fragility curves of overall system and individual components of regular and irregular box-girder highway bridges in two cases: with pounding and without pounding. For this purpose, four levels of altitudinal irregularity, ranging from regular to highly irregular, are considered. To extend the results for all bridges in the same class, different sources of uncertainties related to earthquakes, structural geometries, and material properties are taken into account. The analytical fragility curves have been developed based on nonlinear time history analyses in OpenSees finite element software for the cases with and without pounding effects. The process has been repeated for each two-, three-, and four-span classes at four irregularity levels. The fragility function parameters for the two cases with and without pounding have been compared for all classes considered in this study. Using fragility functions, this paper clarifies the interactive roles of irregularity and pounding between deck and abutments for seismic vulnerability of multi-span box-birder highway bridges. The results indicate that collisions often show an adverse effect on all structural components. It has also been observed that the detrimental effect of pounding on seismic fragility is more apparent in irregular bridges when compared with regular ones. In addition, the study introduces a conversion coefficient to clarify the effects of pounding on the fragility of bridge components and the overall system. This coefficient can be applied in both conventional analytical methods like static or simplified analysis and technical earthquake models like HAZUS, adjusting fragility values for pounding and irregularity effects. [ABSTRACT FROM AUTHOR]