Most codes of practice state that for large in-plane structures it is necessary to account for the spatial variability of earthquake ground motion. There are essentially three effects that contribute for this variation: (i) wave passage effect, due to finite propagation velocity; (ii) incoherence effect, due to differences in superposition of waves; and (iii) the local site amplification due to spatial variation in geological conditions. This paper discusses the procedures to be undertaken in the time domain analysis of a cable-stayed bridge under spatial variability of earthquake ground motion. The artificial synthesis of correlated displacements series that simulate the earthquake load is discussed first. Next, it is described the 3D model of the International Guadiana Bridge used for running tests with seismic analysis. A comparison of the effects produced by seismic waves with different apparent propagation velocities and different geological conditions is undertaken. The results in this study show that the differences between the analysis with and without spatial variability of earthquake ground motion can be important for some displacements and internal forces, especially those influenced by symmetric modes.