This study investigated the feasibility of high-risk percutaneous coronary intervention (PCI) in hemodynamically unstable patients supported by modified cardiopulmonary bypass (extracorporeal life support [ELS]). Over a 38-month period, 15 patients (10 men, 5 women, mean age 72 ± 9 years, mean ejection fraction 34 ± 15%, angina pectoris New York Heart Association class III to IV) who were not eligible for coronary artery bypass grafting because of high co-morbidity underwent elective high-risk PCI supported by ELS. All lesions were technically challenging. ELS perfusion cannulas in the femoral artery and vein were surgically inserted and removed. Procedural success was achieved in 14 of 15 patients. After a mean perfusion duration of 88 ± 37 minutes, all patients were weaned from the ELS in the catheterization laboratory. The patients were ventilated for 5.1 ± 3.3 hours. Blood transfusion was given to 8 patients. Apart from 2 groin bleedings, no other complications occurred. Patients left our hospital after 3.2 ± 2.8 days. Of the 4 patients who died during the 15 ± 12-month follow-up, 1 died of a noncardiac cause. In conclusion, in highly selected patients ineligible for bypass surgery, ELS-supported PCI can be performed with promising short- and long-term clinical outcomes. This complex procedure is a safe alternative whenever other options for revascularization are exhausted.