Failure of a microvascular free flap remains rare, yet multiple failures can occur, particularly in the presence of hypercoagulable conditions. This case series highlights our experience with a rare hypercoagulable state: hyperhomocysteinemia. We present two cases of patients with hyperhomocysteinemia in this report. High-dose heparinization was administered to both patients, resulting in successful salvage of one flap and failure of the other. Notably, one patient had a history of prior free flap failures. However, after correcting hyperhomocysteinemia, subsequent free flaps were successful. In cases of detected complications, a coagulability study is warranted, and adjustments to anticoagulation treatment may be necessary. Furthermore, when a history of flap failures is evident, screening for hyperhomocysteinemia may be warranted, with correction made prior to reconstruction.