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In this report, we present our experience with subcutaneous rt-PA injection for salvage of free radial forearm flaps with vascular compromise. Three patients underwent reconstruction of defects of the soft palate or the lateral tongue with a free radial forearm flap. Patients underwent on average two attempted operative revisions with thrombectomy and intravenous heparin injections. After recurrent venous thrombosis 3–6 days after surgery, rt-PA (Alteplase 2 mg; 1,160,000 IE) was injected subcutaneously at multiple sites into the compromised flap as final attempt. In all three patients, successful thrombolysis with no or only partial soft tissue loss was achieved after subcutaneous injection of rt-PA. We therefore suggest subcutaneous rt-PA injection as an additional tool in managing difficult and recurrent cases of venous thrombosis in free flap head and neck reconstruction. © 2013 Wiley Periodicals, Inc. Microsurgery 33:478–481, 2013.