Background/Synopsis: Myocardial infarction and ischaemic stroke remain the leading cause of mortality both in Australia and worldwide. Whilst therapeutic advances using anti-platelet and anticoagulation drugs have been made to address these statistics, they have significant drawbacks, including bleeding complications. Therefore, their use is highly restricted leaving many patients untreated. Objectives/Purpose: Our aim was to develop a targeted anti-thrombotic therapy to deliver a therapeutic payload directly to the site of the thrombus, thereby preventing bleeding side effects Methods/Results: Flow cytometry assays using both human and mouse blood demonstrated the binding affinity of Targ-TAP specifically to platelets that were activated using ADP, CRP or TRAP, while no binding was observed with Mut-TAP (p<0.05). Light transmission aggregometry demonstrated strong platelet inhibition using Targ-Tap but no inhibition using Mut-TAP (p<0.05). Flow chamber assays using bright field microscopy demonstrated the potent anticoagulant capacity of Targ-TAP (Figure 1), as well as its specificity toward aggregated platelets (p<0.05). Furthermore, therapy using Targ-TAP significantly inhibit thrombosis in murine models of both arterial (Figure 2) and venous thrombosis. Prophylactic protection, against both arterial and venous thrombosis, was achieved by subcutaneous injection of Targ- TAP (4 hours and 24 hours) prior to injury (Figure 3). More importantly, Targ-TAP does not increase bleeding time nor blood volume loss. (The form abridges) Conclusion: Targ-TAP allows for the enrichment of the anticoagulant effect directly at the site of the developing thrombus, whilst ensuring low systemic concentrations. Targ-TAP represents a novel, effective and safe anticoagulant drug candidate. The recombinant character of this drug allows tailoring of the pharmacokinetic (e.g. different molecular weights) ready either for intravenous or subcutaneous injections.