In 2005, the investigators described a "hybrid" cardiovascular interventional strategy combining percutaneous coronary intervention (PCI) for coronary artery disease (CAD) followed by valve surgery for patients with urgent complex CAD and valve disease to reduce morbidity and mortality. This hybrid approach has been extended prospectively in elderly, high-risk patients with aortic stenosis scheduled for elective minimally invasive aortic valve replacement (MI-AVR) who, on preoperative coronary angiography, were found to have moderate CAD amenable to PCI. In this prospective, observational series, 18 patients (mean age 76 years) underwent elective hybrid MI-AVR with PCI from May 2003 to February 2006. Five patients had undergone previous coronary artery bypass grafting. Patients underwent coronary angiography the day of (n = 12) or evening before (n = 6) MI-AVR, and after identifying moderately severe CAD, all 18 underwent the implantation of drug-eluting stents to the affected coronary arteries, followed by MI-AVR. Although all patients received standard doses of antiplatelet medications, including acetylsalicylic acid (325 mg before PCI and 325 mg/day thereafter) and clopidogrel (300 mg after PCI, 75 mg/day thereafter for 90 days for the Cypher stent), there were no reoperations for bleeding; only 8 of 18 patients required postoperative blood transfusions. One patient died postoperatively from a colonic perforation, and there were no late mortalities after a mean follow-up of 19 months. In conclusion, this hybrid strategy has low morbidity and mortality and may be a new therapeutic option for older, high-risk patients with combined CAD and aortic valve disease.