The use of recombinant tissue plasminogen activator (rTPA) in microvascular surgery has been previously reported, but no consensus exists regarding its indications, dose, efficacy, or safety. The records of all patients undergoing free tissue transfer at one institution between 2000 and 2005 were reviewed. Patients requiring reexploration for pedicle thrombosis were identified. Chi-square and the two-sided Fisher's exact tests were used to compare differences between the two groups. Two hundred seventy-five free flaps were performed in 259 patients. In 27 cases (10 percent), reexploration for impending failure was performed, and pedicle thrombosis was observed in 22 cases. In 15 cases, rTPA was administered. Ten of these flaps (67 percent) were successfully salvaged, compared to 2/7 (29 percent) in the no-rTPA group. Heparin was used in 12 patients but was not associated with a higher salvage rate. These findings suggest that the isolated perfusion of rTPA in the salvage of the failing free flap may be more effective than anastomotic revision alone and should be considered when vascular thrombosis is encountered on reexploration of the failing free flap.