Spray simulation using Lagrangian Droplet and Eulerian Fluid (LDEF) method and the Discrete Droplet Model (DDM) has been proved to be of grid dependency. The grid effects on the spray simulation of an asymmetric three hole nozzle were studied. First, the sources of grid dependency were analyzed. The effects of grid types and different grid sizes of radial, azimuthal and axial directions on the spray process were investigated by comparing the spray shape and liquid penetration distance with experiment data. And the grid effect on the Sauter Mean Diameter (SMD) was studied. Finally, the aspect ratio between the radial and the axial directions of the grid was optimized. The result has shown that, for the asymmetric three hole nozzle spray simulation, the polar mesh has better performance among the different mesh forms. With the decrease of the grid size on three directions, the spray tip penetration and SMD basically present the tendency of increase, while the radial grid size shows greater influence than the axial size. The spray tip penetration fits best with experimental data when the grid size and the aspect ratio are optimized.