Puymirat E, Nakache A, Etienne CS, et al. - In the era of modern reperfusion and optimized secondary prevention, whether the difference in prognosis based on number of vessel disease in ST‐elevation myocardial infarction (STEMI) patients has decreased was investigated herein, given that STEMI with multivessel disease (MVD) is associated with a worse prognosis. This analysis involved 1,886 patients (mean age 62.2 ± 14.0 year; 74% of male) with STEMI receiving primary percutaneous coronary intervention (PCI) within 24 h of symptoms onset, recruited from the CRAC (Club Régional des Angioplasticiens de la région Centre) France PCI registry. In one‐, two, and three‐VD, the rate of major adverse cardiovascular events (MACE, defined as all‐cause death, stroke or re‐myocardial infarction) at 1 year was estimated to be 10%, 12%, and 12%, respectively. Two‐ and three‐VD, vs single VD, were not related to higher rate of MACE in multivariable adjusted Cox proportional hazard regression model. Overall, findings showed that despite still representing an essential proportion of STEMI patients, MVD was not related to worse clinical outcomes at 1‐year in these patients vs one‐VD patients in a modern reperfusion area and secondary medication prevention.