This article reviews the context and evidence of recent myocardial revascularization trials that compared percutaneous coronary intervention with coronary artery bypass grafting for the treatment of left main and multivessel coronary artery disease. We develop the rationale that some of the knowledge synthesis resulting from these trials, particularly with regard to the claimed noninferiority of percutaneous coronary intervention beyond nondiabetic patients with low anatomic complexity, may have been affected by trial design, patient selection based on suitability for percutaneous coronary intervention, and end point optimization favoring percutaneous coronary intervention over coronary artery bypass grafting. We provide recommendations that include holding a circumspect interpretation of the currently available evidence, as well as suggestions for the collaborative design and conduct of future clinical trials in this and other fields.