Due to the flexibility of one-side-supported thin impeller blades, machining defects such as overcut or undercut frequently occur, especially at the front and rear edge connecting the suction surface and the pressure surface, where the thickness are even less than 0.2 millimeter. Vibration and deformation are great challenges for engineers and should be mitigated for better quality. To this end, in the paper a method of tool orientation determination for vibration and deformation reduction during ball-end milling of flexible impeller blades is proposed. In order to reduce vibration level, carefully at the front and rear edge, the direction of resultant cutting force is attempted to be adjusted in the plane in which the stiffness of blade is relatively high. Thus, the cutting force component in the direction of high flexibility is small enough. As a result of modeling, two parts are included, i.e. modeling of tool-workpiece engagement and cutting force in the ball-end finish milling, FEM modeling of structure deformation of flexible workpiece. Machining experiments on 5-axis machining center Mikron UCP 800 verify that the optimized tool orientation could be used for deformation and vibration reduction in milling of flexible parts.