Vascular injury may result from both trauma and invasive medical procedures. High‐intensity focused ultrasound (HIFU) was used to occlude surgically exposed blood vessels of anesthetized rabbits, as a mechanism of hemostasis applicable to vascular injury. A HIFU transducer, with a spherically curved aperture area of 6.34 cm2, a focal length of 4 cm, and a frequency of 3.3 MHz, was used. The transducer was equipped with a conical housing filled with water, providing a coupling medium to the vessels. Femoral arteries and veins were occluded after a HIFU treatment of approximately 30–60 s, at a focal intensity of 3000 W/cm2. The vessels were severed after the treatment to confirm complete occlusion. No bleeding was observed. Gross and microscopic examination of the vessels revealed two major mechanisms of occlusion, dissection of the vessel wall and shrinkage of the vessel. In the dissection mechanism, a flap of the inner wall of the vessel peeled as a result of the HIFU treatment and caused a blockage of the blood flow, while in the shrinkage mechanism a mechanical constriction of the vessel lumen caused the blockage. HIFU may provide a valuable method for hemostasis of injured vessels by treating a region of the blood vessel, proximal to the hemorrhaging site.