The Curvilinear Hydrodynamic 3-D with vertical sigma coordinate (CH3D-S) model developed by Sheng (1986) is routinely applied in 3-D hydrodynamic and water quality modeling studies at the Engineering Research and Development Center (ERDC), Mississippi. Recent model improvements include the spatially and temporally varying wind and wave radiation stress gradient forcing. The practical applications of the original single-block version of CH3D-S, which include the aforementioned model improvements have been limited to small computational domains and short simulation time periods, due to long computational processing time as well as large memory requirements. Critical to elimination of these restrictions was the implementation of a multi-block grid generation and Message Passing Interface (MPI) by Luong and Chapman (2009). The advantages of the multi-block grid parallel version of CH3D-S include the flexibility of site specific horizontal and vertical grid resolution assigned to each grid block, reduced memory and computational time requirements allowing larger computational domains and longer simulation time periods. The Hydrodynamic Modeling of Deer Island, Biloxi Bay, and Adjacent Mississippi Sound for Deer Island Ecological Restoration was used for demonstrating the advantages of the parallel computing using multi-block grid technique in this study. A comparison of multi-block grid predictions of water levels, salinity/temperature time series is presented. CPU wall-clock times of multi-block grid on several HPC computer systems are presented.