Purpose: Recent studies have reported on application of fibrin glue composed of fibrinogen and thrombin to nerve anastomosis, which can be another candidate for vessel anastomosis. However, no research regarding the risk and effectiveness of thrombin in microvascular free tissue transfer has been reported. Therefore, the aim of study is to determine the risk and effectiveness of thrombin on microvascular free tissue transfer through clinical cases. Materials and Methods: Twenty-five patients underwent free flap reconstruction for soft tissue defect or bone exposure in our institute from March 2011 to February 2014. In the group using thrombin, dissolved powder thrombin (5,000 IU/amp) was mixed with 10 mL normal saline. Saline mixed with thrombin was applied on the flap, recipient, and around vessel anastomosis. In the control group, free flap was performed using the same method, except using thrombin. We analyzed the results between the two groups. Results: All flaps survived. The group using thrombin included 14 patients and the control group included 11 patients. Hematoma was found in two cases, respectively, in each group. The group using thrombin showed lower incidence of hematoma than the control group. No difference in survival rate of the flap was observed between the thrombin group and the control group. Conclusion: Results of this study showed that use of saline mixed with thrombin in free tissue transfer may be safe and effective for prevention of hematoma formation in the recipient site.