The multi-dimensional and multi-point random acceleration time histories considering the spatial correlation and non-stationary characteristics of the ground motion field are synthesized artificially, and then the absolute displacement input method, which is convenient, accurate and most suitable for nonlinear analysis of isolated structures, is used to calculate the seismic response of large span isolated grid structures under the multi-dimensional and multi-point excitation or the multi-dimensional and uniform excitation. At last, the structural span and apparent wave velocity are taken as the main variables to investigate the difference of horizontal and vertical seismic responses of the truss roof of the large span isolated structures under two seismic input modes systematically. The results show that the multi-point input effect of large span isolated structures weakens gradually with the increase of apparent wave velocity. When the apparent wave velocity reaches 500m/s, the multi-point input effect can be neglected, and then the limit of apparent wave velocity is obtained. The multi-point input effect strengthens gradually with the increase of the span, and the upperSandSlowerSlimits of structural span is 60m and 120m in which cases the effect can be ignored and must be considered. With the increase of structural span, the isolation effect of horizontal deformation of structures has a general tendency of becoming better, but there is no obvious vertical isolation effect. Those nodes near the boundary supports of the large span truss roof have greater responses after the isolation, which should be strengthened in the engineering design.