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The objective was to investigate the long-term efficacy of hemostasis and healing of arteries after HIFU application. The femoral arteries of 22 adult rabbits were surgically exposed. Fifteen arteries were punctured with a needle and treated with HIFU, and 7 arteries were sham-treated (no puncture or HIFU was applied). The tip of the HIFU applicator was positioned on the bleeding site, and HIFU energy was applied until hemostasis was achieved. The focal intensity was approximately 3,000 W/cm2, at the resonant frequency of 9.6 MHz. Serial ultrasound images, blood and tissue samples were collected immediately and on days 1, 3, 7, 14, 28, and 60 after the treatment. Eleven of the arteries were patent after the treatment, and four arteries were occluded, as confirmed using Doppler imaging. One of the occluded arteries reopened at day 14. HIFU exposure time to achieve hemostasis was 27 ±17 seconds for patent arteries and 101±38 seconds for the occluded arteries. The blood flow velocities were not statistically different between HIFU-treated patent vessels and sham-treated vessels. The tunica adventitia and media, disrupted and coagulated immediately after the treatment, recovered to normal appearance within 28 days, with localized thinning of the tunica media observed up to day 60. Neo-intimal hyperplasia was observed in the arteries at days 14 and 28. HIFU produced an effective and long-term (up to 60 days) hemostasis of injured femoral arteries while preserving a normal blood flow and vessel wall structure in the majority of vessels. © 2005 American Institute of Physics [ABSTRACT FROM AUTHOR]