Irradiation commonly is used after resection of soft tissue sarcomas to decrease the local recurrence rate. Brachytherapy spares more normal tissue than external beam irradiation and permits irradiation to the tumor bed in the immediate postoperative period. After vascular anastomosis and irradiation, flap survival can be affected by vascular coagulation in the immediate postoperative period and later by vascular fibrosis secondary to irradiation effects. The purpose of the current retrospective study was to evaluate the survival of free tissue transfer when combined with brachytherapy after resection of soft tissue sarcomas. Thirty-six patients had wide resection of extremity tumors, free flap coverage, and brachytherapy 5 days after surgery. Followup averaged 54 months. There were three major and four minor complications. The major complications included two patients with free flaps who required revision of anastomosis before radiation therapy (they had brachytherapy 5 days after the second surgery without additional complications) and one patient who had a deep wound infection develop 2 months after the index procedure and required a second flap. Minor complications included one hematoma, one partial skin graft loss, and two superficial infections. Brachytherapy can be done safely at the site of microvascular anastomosis in the immediate postoperative period.