Plaque disruption and thrombosis are the most important pathogenetic mechanisms of acute coronary syndrome (ACS). Although unfractionated heparin (UFH) was the standard antithrombotic agent for the treatment of ACS, low-molecular-weight heparins (LMWH) are an effective alternative antithrombotic therapy for its more favorable pharmacokinetic and pharmacodynamic profile, and several clinical advantages. Some studies have assessed LMWH in comparison with UFH in patients with ACS, but enoxaparin is the only LMWH to have demonstrated significant clinical and economic benefits in this setting of patients. A recent meta-analysis of ESSENCE, TIMI 11B trial, INTERACT, A to Z and SYNERGY studies has shown that enoxaparin is more effective than UFH in preventing the combined endpoint of death or myocardial infarction in ACS without ST-segment elevation. Moreover, the results of ENTIRE-TIMI 23, ASSENT-3 and the recent ExTRACT-TIMI 25 have demonstrated that adjunctive antithrombotic therapy with enoxaparin, compared with UFH, reduces the composite endpoint of all-cause mortality or non-fatal reinfarction within 30 days in patients with ST-elevation myocardial infarction who are eligible to receive fibrinolytic therapy.