This study evaluates the efficacy of our protocol using intra-arterial infusion of tissue plasminogen activator (TPA) on free flap salvage following venous thrombosis. A retrospective review was conducted of every free flap performed by a single surgeon since the beginning of his practice. Free flap salvage rates were documented following flap exploration, intra-arterial infusion of TPA, and revision of the venous anastomosis, with or without vein grafting. One hundred twenty-two free tissue transfers were performed from July 2003 through April 2006. Twelve anastomotic complications occurred in 11 flaps (1 arterial thrombosis, 11 venous thromboses). One free muscle flap failed due to arterial thrombosis. All venous thromboses were salvaged using the TPA protocol, although one revision thrombosed on postoperative day 1 and required a second venous revision, leading to its ultimate salvage. We believe that intra-arterial TPA is an effective adjunct in the treatment of microsurgical venous thrombosis and may increase salvage rates following anastomotic complications.