Abstract: In consideration of the bearing stiffness, the contact deformation between the ball screw and the worktable, and the contact deformation between the worktable and the guide, lateral, longitudinal and torsional vibration of the preload screw and vibration of the worktable are studied. Dynamic model of the ball screw drive system of machines is established using Lagrange equation. The model is analyzed by the mode superposition and Runge-Kutta method to calculate the transient response of the system. From the orthogonal experiment, effect of the system parameters on axial vibration of cutters' work point is studied, yielding the optimistic system parameters for the minimum vibration. The present work supplies a base for designing the drive system.