Observational studies, randomized controlled trials (RCTs), and meta-analyses comparing culprit artery only PCI with multivessel PCI have reported conflict- likely because of differing inclusion criteria, study protocols, timing of multivessel PCI, statistical heterogeneity, and variable endpoints (Data Supplement). Previous clinical practice guidelines recommended against PCI of nonculprit artery stenoses at the time of primary PCI in hemodynamically stable patients with STEMI.9,10 Planning for routine, staged PCI of noninfarct artery stenoses on the basis of the initial angiographic findings was not addressed in these previous guidelines, and noninfarct artery PCI was considered only in the limited context of spontaneous isch- emia or high-risk findings on predischarge noninvasive test- ing. The earlier recommendations were based in part on safety concerns, which included increased risks for procedural com- plications, longer procedural time, contrast nephropathy, and stent thrombosis in a prothrombotic and proinflammatory and in part on the findings from many observational studies and meta-analyses of trends toward or statistically sig- nificant worse outcomes in those who underwent multivessel Four RCTs have since suggested that a strategy of multi- vessel PCI, either at the time of primary PCI or as a planned, staged procedure, may be beneficial and safe in selected patients with STEMI17,18,24,27 (Data Supplement). In the PRAMI (Preventive Angioplasty in Acute Myocardial Infarction) trial the composite primary outcome of cardiac death, nonfatal myocardial infarction (MI), or refractory angina occurred in 21 patients (9%) treated with multivessel primary PCI, compared with 53 patients (22%) treated with culprit artery only PCI (HR: 0.35; 95% CI: 0.21 to 0.58; P<0.001). In the CvLPRIT (Complete Versus Culprit-Lesion Only Primary PCI) trial,18 296 patients were randomized to culprit artery only or multivessel PCI during the index hospitaliza- tion (72% underwent multivessel primary PCI). 