An approach for the lightweight design of a 3-DOF spindle head—A3 head designed for high-speed milling of large aircraft structural components is presented. The approach can be implemented by two steps: ① formulation of the compliance bounds in the local coordinate system according to the processing parameters for high-speed milling,② minimization of the overall weight of the movable components subject to the compliance and geometrical constraint using the response surface method and the multi-island genetic algorithm (MIGA) integrated in iSIGHT. Compared to the original design,the simulation results show that the compliance of the system can be decreased by more 50%,and the first order frequency can be increased by 30% at the cost of increasing the weight of movable components by just 3.6%. The approach has been successfully employed to design the equipment.