The ball screws are the machine component most frequently used for transforming rotational into linear motion of a feed drive, to position the machine tool components carrying the cutting tool to the desired location. A failure of the ball screw usually leads to a total breakdown of the axis; therefore, the attainable life of this component is an important issue concerning the availability and productivity of modern machine tools. This article presents an approach to evaluate the influence of control parameters on the fatigue life of ball screws based on simulation, by means of a numerical model of a machine tool servo-axis. Ball screw life was evaluated with different conditions, varying the position loop main proportional gain and the kinematic limit conditions for trajectory generation. Furthermore, the mathematical model was used to evaluate optimal control gain and trajectory conditions for a machine tool based on the achievable life span of the ball screw feed drive system, with regard to the desirable performances, such as position accuracy, promptness, and cutoff frequency.