Objective To evaluate the clinical efficacy, safety and prognosis of fondaparinux in patients with non-ST elevation acute coronary syndromes (NSTE-ACS). Methods A retrospective analysis was performed on 2448 NSTE-ACS patients [1696 males, aged 21～90 years, mean (68.4±12.1) years] who were administrated with fondaparinux after receiving either percutaneous coronary intervention (PCI) or merely drug therapy in our department between March 2010 and December 2011 and with intact follow up . We summarized the characteristics of the patients, recorded incidence of in-hospital major bleeding, platelet reduction and incidence of major adverse cardiac events (MACE) during hospitalization and 1 month after discharge. Then we compared our results with those of OASIS-5 trial. Results There was no significant difference between our study and OASIS-5 in baseline clinical characteristics (P＞0.05). The success rate of the invention operation was 97.1% (2043/2104). There was no death during the PCI procedure. Compared with OASIS-5 trial, which used enoxaparin to assist anticoagulation for patients with NSTE-ACS, our study showed identical incidence of death, myocardial infarction and refractory ischemia at day 9 and day 30, while fondaparinux group showed significantly lower incidence of major bleeding than enoxaparin group at day 9 (P＜0.05). The incidence of major bleeding in fondaparinux group was significantly lower than that in enoxaparin group in OASIS-5 at day 9 (1.6% vs 4.1%; HR: 0.38; 95% CI: 0.28?0.54; P＜0.05), and this difference continued during the 30 days follow-up (1.4% vs 5.0%; HR: 0.65; 95% CI: 0.45?0.93; P＜0.05). Incidence of bleeding complication was significantly higher in Tirofiban-used patients than in non-Tirofiban-used ones (25.6% vs 3.8%, P＜0.001). Patients with renal impairment mainly manifested with multivessel lesions identified by coronary angiography. They also showed lower rate of TIMI grade 3 after PCI procedure (21.0%), and higher rate of in-stent thrombosis (1.2%). The incidence of death, myocardial infarction and refractory ischemia of patients with impaired renal function at day 9 were significantly higher than those in patients with normal renal function (4.94% vs 1.04%; HR: 7.87; 95% CI: 3.41?18.16; P＜0.05), and this difference sustained during the 30 days follow-up (5.4% vs 2.4%, P＜0.05). Patients with renal impairment in fondaparinux group had significantly reduced incidence of major bleeding than those in enoxaparin group of OASIS-5 trial (2.2% vs 6.4%; P＜0.001). Conclusion Application of fondaparinux is safe in NSTE-ACS patients both receiving PCI and merely drug therapy. It also significantly improves coronary blood supply and coronary perfusion after PCI procedure as well as clinical prognosis without increasing bleeding risk.