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Steel and steel-concrete composite highway bridges are subjected to traffic-induced dynamic actions which interact with the pavement surface roughness, leading the structural system to experience variable levels of stresses. These dynamic actions may initiate the nucleation of fractures or even cause their propagation along the structure. This way, work aims to develop an analysis methodology for the study of the structural dynamic response, as well as the assessment of the fatigue life of steel-concrete composite highway bridge decks, considering the effect of the partial steel-concrete interaction. For this purpose, within this study, an adequate statistical treatment of the results obtained from the structural analysis, in the time domain, is considered. The investigated structural system is based on a simply supported steel-concrete composite highway bridge spanning 40 meters. Thus, a finite element model, developed for the composite bridge dynamic analysis, adopted the usual mesh refinement techniques present in finite elements method (FEM) simulations, and was implemented in the ANSYS software. An extensive parametric study is developed in order to identify, qualitatively and quantitatively, the effect of the pavement surface roughness on the dynamic structural behavior of the investigated bridge. In the sequence, the verification of the fatigue life of the composite structural system, with partial interaction, is performed, based on the use of Rainflow cycle counting algorithm and S-N curves associated with the European standard EUROCODE EN 1993-1-9. The results obtained based on the numerical analyses are investigated and a fatigue analysis is performed for some proposed structural details related to the bridge design.