Primary percutaneous coronary intervention (PCI) is currently the preferred revascularization strategy in acute trasmural myocardial infarction (AMI). In this setting, about one half of patients will be diagnosed with concomitant multivessel (MV) coronary artery disease, associated with a multitude of negative prognostic factors but also still an independent predictor of adverse cardiac events and increased long-term mortality. Since additional "angiographic" lesions found at primary PCI are not directly responsile for the acute presentation, their treatment represents a difficult decision-making problem in cardiology. The article summarizes available clinical data on treatment in this setting and also review our current understanding of short-term progression of atherosclerosis after AMI.