In a previous study, several computational fluid dynamics (CFD) simulations of fuel assembly thermal-hydraulic problems were presented that contained fewer fuel rods, such as 3 × 3 and 5 × 5, due to limited computer capacity. However, a typical AFA-3G fuel assembly consists of 17 × 17 rods. The pressure drop levels and flow details in the whole fuel assembly, and even in the pressurized water reactor (PWR), are not available. Hence, an appropriate CFD method for a full-scale 17 × 17 fuel assembly was the focus of this study. The spacer grids with mixing vanes, springs, and dimples were considered. The polyhedral and extruded mesh was generated using Star-CCM+ software and the total mesh number was about 200 million. The axial and lateral velocity distribution in the sub-channels was investigated. The pressure distribution downstream of different spacer grids were also obtained. As a result, an appropriate method for full-scale rod bundle simulations was obtained. The CFD analysis of thermal-hydraulic problems in a reactor coolant system can be widely conducted by using real-size fuel assembly models.