In this study, different designs of the opening pattern of computer fan grills were investigated. The objective of this study was to propose a simulation analysis and compare it to the experimental results for a set of optimized fan designs. The FLUENT computational fluid dynamics (CFD) simulation software was used to analyze the fan blade flow. The experimental results obtained by the simulation analysis of the optimized fan designs were analyzed and compared. The effect of different opening pattern designs on the resulting airflow rate was investigated. Six types of fans with different grills were analyzed. The airflow velocity distribution in the simulated flow channel indicated that the wind speed efficiency of the fan and its influence were comparable with the experimental model. The air was forced by the fan into the air duct. The flow path was separately measured by analog instruments. The three-dimensional flow field was determined by performing a wind speed comparison on nine planes containing the mainstream velocity vector. Moreover, the three-dimensional curved surface flow field at the outlet position and the highest fan rotation speed were investigated. The air velocity distribution at the inlet and the outlet of the fan indicated that among the air outlet opening designs, the honeycomb shaped air outlet displayed the optimal performance by investigating the fan characteristics and the estimated wind speed efficiency. These optimized designs were the most ideal configurations to compare these results. The air flow rate was evenly distributed at the fan inlet.