Abstract We assessed the short‐term outcome of percutaneous coronary ultrasound thrombolysis (CUT) for high‐risk thrombus‐containing lesions in native coronaries in the setting of acute coronary syndromes (ACS). Data were prospectively collected in a multicenter (n = 32) registry of consecutive ACS patients. The study population (n = 126) had mostly (84%) totally occluded vessels. The mean age of clot was 5.7 ± 9.5 days (range, 0–60 days). CUT (41 kHz, 18 W) led to device success in 112 (89%) patients, with a residual stenosis of 69% ± 20%. Adjunct PTCA or stenting was used in 97% of the patients. Procedural success was achieved in 124 (98%) patients, with a final residual stenosis of 6% ± 10%. There were no major adverse clinical events during hospitalization. Ultrasound thrombolysis is a feasible procedure that offers a safe and probably effective adjuvant device solution for the treatment of high‐risk, thrombus‐containing lesions in the native coronary arteries. Cathet Cardiovasc Intervent 2002;55:43–49. © 2002 Wiley‐Liss, Inc.