Free-tissue transfer has become routine surgery because of standardization of instrumentation, techniques, and training. The incidence of microvascular thrombosis leading to free-flap failure is relatively low; however, anastomotic thrombosis can still occur despite the best of circumstances. Although majority of the time it is due to technical mishap or misjudgment, free-flap failure can occur due to intrinsic factors, such as the patient's increased propensity to develop clots. We describe a case report of a patient with malignancy and multiple thrombophilias, which led to 2 successive failures in microvascular flap transfer to restore abdominal domain. The aim o f this article is to increase awareness of the potential for thrombophilias to cause a dismal outcome in free-tissue transfer. A review of the literature will be presented, and published cases of free-flap failure in patients with thrombophilia(s) will be summarized.