We studied the safety and feasibility of intracoronary sonotherapy (IST) and its effect on the coronary vessel at 6 months. Thirty-seven patients with stable or unstable angina were included (40 lesions). The indication was de novo lesion (n = 26), restenosis (n = 2), in-stent restenosis (n = 11), and a total occlusion of a venous bypass graft. After successful angioplasty, IST was performed using a 5 Fr catheter with three serial ultrasound transducers operating at 1 MHz. IST was successfully performed in 36 lesions (success rate, 90%). IST exposure time per lesion was 718 ± 127 sec. During hospital stay, one patient died due to a bleeding complication. At 6-month follow-up, one patient experienced acute myocardial infarction, eight patients underwent repeat PTCA. No patient underwent CABG. Late lumen loss was 1.05 ± 0.70 mm with a restenosis rate of 25%. IVUS analysis revealed a neointima burden of 25% ± 11%. IST can be applied safely and with high acute procedural success. Sonotherapy-related major adverse events were not observed. Late lumen loss and neointimal growth were similar to conventional PTCA approaches. These results justify the initiation of randomized clinical efficacy studies. Catheter Cardiovasc Interv 2003;60:9–17. © 2003 Wiley–Liss, Inc.