Scientific evidence that prognosis of patients with ischemic heart disease, treated by either surgery or percutaneous revascularization, is similar, has led interventional cardiologists to search for an aggressive approach in percutaneous revascularization of patients with multivessel disease. It is still matter of debate which strategy is preferable between pursuing complete revascularization or performing revascularization of the culprit vessel and later of the other vessels. According to American and European guidelines for percutaneous coronary intervention (PCI) in patients with acute coronary syndromes with ST-segment elevation and multivessel disease, primary angioplasty should only be directed to the infarct-related artery (culprit vessel), with decision about PCI of non-culprit lesions guided by objective evidence of residual ischemia at later follow-up. PCI should not be performed in a non-infarct-related artery at the time of primary angioplasty in patients without hemodynamic impairment. In patients with acute coronary syndromes without persistent ST-segment elevation the decision to perform either culprit vessel or complete revascularization can be made on individual basis; in patients with favorable anatomy, the competent practitioner can perform either single or multivessel PCI with a high likelihood of success and low risk of morbidity and mortality. The endothelial dysfunction induced by coronary angioplasty, the occurrence of post-procedural infarction and contrast-induced nephropathy, the X-ray exposure, the problem of the informed consent, the procedural costs are aspects that strongly support a strategy based on staged revascularization when appropriate.