Guidewires for endovascular interventional surgery are inevitably affected by high frictional resistance because of direct contact with the vascular wall, which greatly reduces the operation efficiency and safety. This article presents a method of applying radial ultrasonic microvibration at the proximal end of a conventional passive guidewire to reduce the frictional resistance. The proposed method theoretically reduced the frictional resistance by reducing the friction coefficient, actual contact area, and the net friction time between the guidewire and vascular wall. The effectiveness of the proposed method was experimentally demonstrated in designed simulations of the blood vessel environment, where the influences of the vibration amplitude on the drag reduction effect were considered. The results indicated that vibrating the guidewire at the resonant frequency with the designed device clearly reduced the drag with a maximum frictional reduction rate of 85.19%. At the resonant frequency, the change in frictional resistance showed a linear negative correlation with the applied vibration amplitude. The proposed method offers a new approach to improving the efficiency and safety of vascular interventional surgery.