Despite the use of lytics, aggressive antiplatelet agents, stents and thrombectomy devices, intracoronary thrombus remains a challenge for interventional catheter-based techniques, mainly due to insufficient reduction of thrombus and risk of distal embolization. This study assesses the clinical safety and efficacy of the X-SIZER catheter (EndiCOR Medical, Inc., San Clemente, California), a novel device designed to remove soft atherothrombotic tissue from native coronary arteries, saphenous vein grafts and restenotic stents. The X-SIZER was used during catheter-based intervention as the initial device in patients with angiographically suspected thrombus at the target. Inclusion criteria were target lesion stenosis of > or = 70% diameter stenosis (DS) or > or = 50% DS with Thrombolysis in Myocardial Infarction (TIMI) flow reduction and a reference diameter of 3 mm. Analyses were performed for reduction of stenosis, improvement of TIMI flow grade by X-SIZER alone (X-SIZER outcome) and after final adjunct procedure (final outcome), angiographic complications (dissection, embolization, perforation), adverse clinical events during hospitalization, and device-related technical failures. Eighty-five patients (age range, 31-82 years old; 69 male) were studied. Forty-four patients with unstable angina and 31 with acute myocardial infarction (MI) were treated, including 18 saphenous vein grafts and 17 re-occluded stents. In 71/85 patients (84%), the X-SIZER reached the target lesion and was successfully activated. Technical failures were associated with tortuous anatomy or vessel caliber < 3 mm. In 60/71 patients (85%), X-SIZER success was achieved by either improving TIMI flow by at least one grade or reducing DS by at least 20% (DS pre-X-SIZER = 88 +/- 19%; DS post-X-SIZER = 60 +/- 29%) without a major adverse clinical event (i.e., death, Q-wave MI, three-fold elevation of creatine kinase, or total occlusion or perforation requiring emergency bypass surgery or emergency stenting). Creatinine kinase rise greater than 3 times baseline occurred in 2 patients without preexisting acute MI. Thrombus dislodgement occurred in 3 patients and vessel perforation without clinical sequelae occurred in 1 patient. No other major procedural complications were noted. Adjunct interventions (balloon and stent) were employed in all except two X-SIZER stand-alone cases for a final DS of 11 +/- 18%. The X-SIZER Catheter System is simple to use, safe and effective for patients with relatively large, non-tortuous target vessels. Improved catheter characteristics may expand its use to more complex anatomy.