The milling of highly flexible workpieces, such as thin-walled structures used in turbine blades, aerospace equipment, and jet engine compressors, requires vibration compensation to improve the quality of the workpiece surface. Vibration can be reduced by selecting appropriate cutting parameters. However, this approach reduces system productivity. This paper presents an active workpiece holder that controls the vibration of general computer numerical control machine tools. The proposed holder, which comprises a flexible guide mechanism, driver, and sensor, measures vibration and actively controls it using piezoactuators. A high-rigidity flexure mechanism was designed for the holder, and finite element method simulation and modal analysis were performed. Finally, the proposed system was fabricated, and experimental verification indicated that the system reduced vibration. The surface quality obtained using the controlled system was ∼50% better than that obtained using the uncontrolled system.