Introduction. In the OASIS 6 trial, fondaparinux (fonda) 2.5 mg/day subcutaneously was compared to placebo or i.v. unfractionated heparin in a wide range of patients presenting with acute ST-segment elevation myocardial infarction (STEMI). Overall, fonda significantly reduced mortality and reinfarction at 30 days (9.7 vs 11.2%, p=0.008) without increasing bleeding or strokes. Results were heterogeneous in subgroups based on type of reperfusion therapy, such that no benefit was observed in those patients undergoing primary PCI. We investigated the subgroup of patients who received thrombolytics as the reperfusion strategy. Methods and results. Of the12,092 patients included, 5436 patients (45%) received thrombolytics. Of these, 4415 patients did not have an indication for heparin therapy according to local practice (stratum 1) and 1021 did (stratum 2). In stratum 1, 4395 patients (99.6%) received non-fibrin specific (NFS: streptokinase, urokinase) thrombolytic agents. In stratum 2, 855 patients (83.7%) received fibrin specific (FS: tPA and derivatives) thrombolytics. Consequently, control therapy with NFS lytics was placebo in 96.4%, control therapy with FS lytics was heparin in 97.7%. Outcomes by type of lytic at 30 days are presented in the table, including hazard ratio (HR) and 95% confidence interval (95% CI). Outcomes at 180 days were consistent. The risk of severe hemorrhage was significantly reduced in all subgroups. Results were consistent across different times from symptom onset to randomisation. Conclusion. In STEMI patients treated with thrombolytic agents, fondaparinux significantly improved outcome, with no evidence of heterogeneity by whether or not heparin was used in the control arm. Fondaparinux was associated with a significantly reduced risk of severe hemorrhage, irrespective of the type of thrombolytic, and compared to both heparin and placebo.