In order to raise ability of five-axis CNC machine tools to machine geometrically complex work pieces efficiently and with higher dimensional accuracy, it is necessary to research its mechanical eigenfrequency of mechanical transmission system. A multi-body modeling method for the vibration analyze of ball screw drive system is presented in this paper. To design such a structure properly, an analysis model for the multi-body system needs to be developed to estimate the modal characteristics effectively and properly; the transfer matrix method for the solution of the eigenfrequency problems of ball screw drive system for CNC machine is considered here. The vector–matrix formulizers of motion of multi-body system for this system are given. By using transfer matrix method, the global dynamics equation is not needed in the study of multi-body system dynamics, and it has advantages of a small size of matrix and higher computational speed.