There exists controversy on whether and for how long anticoagulation is necessary after primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI).We aimed to study the impact of prolonged (>24 h) or brief (<24 h) postprocedural anticoagulation on infarct size assessed by cardiac magnetic resonance (CMR) after 30 days as well as on left ventricular ejection fraction (LVEF) and left ventricular (LV) remodeling evaluated by 2D-echocardiography after 9 months from the INNOVATION trial (Clinical Trial Registration: NCT02324348).Of the 114 patients (mean age: 59.5 years) enrolled, 76 (66.7%) received prolonged anticoagulation therapy (median duration: 72.6 h) and 38 (33.3%) patients received brief anticoagulation therapy (median duration: 5 h) after primary PCI. There was no significant difference in infarct size (mean size: 15.6% after prolonged anticoagulation versus 19.8% after brief anticoagulation, P = .100) and the incidence of microvascular obstruction (50.7% versus 52.9%, P = .830) between the groups. Even after adjusting, prolonged anticoagulation therapy could not reduce larger infarct (defined as >75 percentile of infarct size; 19.7% versus 35.3%; adjusted odd ratio [OR]: 0.435; 95% confidence interval [CI]: 0.120-1.57; P = .204). Similar results were observed in subanalyses of major high-risk subgroups. Moreover, follow-up LVEF <35% (3.2% versus 7.4%; adjusted OR: 0.383; 95% CI: 0.051-2.884; P = .352) and LV remodeling (defined as >20% increase in LV end-diastolic volume; 37.1% versus 18.5%; adjusted OR: 2.249; 95% CI: 0.593-8.535; P = .234) were similar between groups.These data suggest that prolonged postprocedural anticoagulation may not provide much benefit after successful primary PCI in patients with STEMI. However, further studies are needed.