Vascular thrombosis remains a dreaded complication of any microvascular procedure, be it composite tissue transfer or replantation of amputated limbs or parts. Despite the tremendous advances in microvascular-related technologies and the accumulated surgical skills, failures caused by occlusion of anastomosed vessels remain a continuous source of frustration to all microsurgeons alike. Several anticoagulation and antiplatelet protocols have been proposed to be used in conjunction with microvascular surgery. More recently, thrombolytic drugs such as urokinase, streptokinase, and thrombolysin have been introduced, yet their systemic effect on hemostasis remains an undesirable side effect. We present our experience with local intra-arterial, intravenous, and soft-tissue injection of recombinant tissue plasminogen acti-vator rt-PA in replantation surgery in three consecutive patients. Arterial thrombi are managed by intra-arterial rt-PA infusion with the catheter placed proximal to the arterial anastomosis. Venous thrombi are best lysed by infusing rt-PA in an engorged vein of the replanted limb. In replanted digits, direct intravenous infusion is not possible. In such situations, injection of rt-PA in the pulp soft tissues may result in successful salvage. We believe this agent also has a role in microvascular composite tissue transfer in preventing free flap failures as well as in salvaging failing flaps.