AbstractIntroduction: Despite high success rates with free‐tissue transfer, flap loss continues to be a devastating event. Flap salvage is often successful if vascular complications are recognized and treated early. However, delayed presentation of flap compromise is an ominous predictor of flap loss. Late free‐flap salvage has been described with poor long‐term results. Catheter‐directed thrombolysis (CDT) has only been described in context with free‐tissue transfer in a case of distal bypass salvage. Objectives: The authors examined the efficacy of highly selective CDT in late salvage of free‐flaps with vascular compromise. Methods: Two patients underwent highly selective CDT after delayed presentation (>5 days) of flap compromise. Patient 1 is a 59‐year‐old woman who underwent delayed breast reconstruction with a free TRAM flap and presented with arterial thrombosis 12 days postoperatively. Patient 2 is a 53‐year‐old man who underwent fibular osteocutaneous free‐flap reconstruction of a floor of mouth defect who developed venous thrombosis 6 days postoperatively. Patient 2 underwent two attempted operative anastamotic revisions with thrombectomies and local thrombolysis prior to CDT. Results: The average time of presentation was 9 days, with the average time to CDT being 9.5 days. Patient 1 had an arterial thrombosis, whereas Patient 2 had a venous thrombosis. Both patients underwent successful thrombolysis after super‐selective angiograms. Continuous infusions of thrombolytic agents were used in both patients for ∼24 h. Average length of stay postCDT was 7 days with no perioperative complications. Long‐term follow‐up demonstrated complete flap salvage with no soft tissue loss. Conclusion: Despite extremely delayed presentation, aggressive CDT was successful in both breast, and head and neck reconstructions with excellent long‐term flap results. CDT appears to be a useful modality in managing difficult cases of free‐flap salvage. © 2008 Wiley‐Liss, Inc. Microsurgery, 2008.