We evaluated the use of both intracoronary ultrasound (ICUS) information and unique balloon characteristics provided by a combined ICUS/variable diameter balloon catheter during coronary interventions to achieve the maximal residual lumen using the least number of devices. In 47 patients, 64 coronary lesions were treated with either sequential percutaneous transluminal coronary angioplasty (PTCA) (n = 40) or stenting (primary [n = 17], secondary [n = 7]). The result after PTCA was judged satisfactory if the lumen cross sectional area (by ICUS) in the lesion exceeded 65% of the mean reference area. Stent implantation was judged according to revised MUSIC trial criteria. PTCA or stenting was successful in all 64 lesions using 47 combination devices and 10 conventional balloons (mean number of balloons per lesion: 0.90). PTCA group: diameter stenosis decreased from 78 +/- 11 to 23 +/- 13% following inflation at 10.3 +/- 3.0 atm. ICUS lumen area was 4.6 +/- 1.9 mm2 (proximal reference: 7.4 +/- 3.3 mm2, distal reference: 5.7 +/- 1.8 mm2) resulting in a residual area stenosis of 28 +/- 15%. Stent group: diameter stenosis was reduced from 77 +/- 14 to 10 +/- 10% after stenting. ICUS defined minimal lumen area in the stent was 8.2 +/- 2.2 mm2 (proximal reference: 8.7 +/- 2.6 mm2, distal reference: 8.0 +/- 2.2 mm2) resulting in a residual area stenosis of 7.2 +/- 14.6%. No patient death, myocardial infarction, or emergency surgery occurred and only one target lesion required re-PTCA during hospitalization. In conclusion, use of a combined ICUS/variable diameter balloon catheter allows a single device strategy for ICUS-guided PTCA and stenting in the majority (84%) of unselected lesions.