Much has been learned over the past several decades regarding thrombophilic conditions. Thrombotic complications, such as deep venous thrombosis, pulmonary embolus, myocardial infarction, and stroke, are sometimes attributed to a diagnosable thrombophilia. Less has been written with regard to their effect on reconstructive outcomes. Fortunately, it is rare to encounter a notable intraoperative thrombophilia while performing reconstructive microsurgery. When this does occur, salvage can be difficult and outcome can be compromised. It is imperative that microsurgeons be knowledgeable of both major and minor thrombogenic conditions to optimize intraoperative outcome and postoperative care. We present a case of a failed free flap for lower extremity reconstruction associated with hyperhomocysteinemia in conjunction with markedly elevated Factor VIII levels.