The determination of AGV vehicle requirements in a manufacturing system has a great impact on the system performance. This paper first defines the AGV vehicle requirement determination as a general optimization problem, and secondly develops a new AGV vehicle requirement determination method capable of effective solving the problem. This method features with the combination of discrete event simulation (DES), sensitivity analysis, fractional factorial design (FFD) and response surface methodology (RSM). Tests and comparisons with other simulation based methods have shown that the proposed method combining the simulation method with analytical method, can make full use of their respective advantages and overcome the defects of existing methods. It is more practical.