Background: Whether low molecular weight heparin (LMWH) is superior or similar to unfractionated heparin (UFH) in the setting of off-label use of drug-eluting stents (DES) in acute non-ST-segment elevation myocardial infarction (NSTEMI) is unclear. We compared the safety and efficacy of LMWH versus UFH in AMI setting in Korea Acute Myocardial Infarction Registry (KAMIR). Methods: A total of 1,749 NSTEMI patients (pts) undergoing percutaneous coronary intervention (PCI) with DES received LMWH (n=943 pts, bid for 5-7 days), or UFH (n=806 pts, a bolus of intravenous UFH 5,000 U, followed by 24,000 U/day infusion for at least 48 hours). The in-hospital complications and clinical outcomes at 7 days and 1 month were evaluated. Results: The treatment with LMWH or UFH showed similar incidences of in-hospital complications including the major and minor bleeding events. Furthermore, these two antithrombotic strategies had similar clinical outcomes including total death, cardiac death, repeat PCI, coronary artery bypass graft (CABG) and total major adverse cardiac events (MACE) at 7 days and 1 month, even though there was a trend toward higher incidence of recurrent myocardial infarction in LMWH group than in UFH group at 7 days (0.4% vs. 0, P=0.066). Multivariate logistic analysis also showed that these two antithrombotic strategies had similar clinical outcomes at 7 days and 1 month, respectively. Conclusions: Either LMWH or UFH usage in acute NSTEMI setting, one of important off-label indication of DES, showed similar safety and efficacy up to one month.