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A significant percentage of patients who undergo segmental mandibulectomy for head and neck cancer will develop a new or recurrent cancer or osteoradionecrosis, necessitating a second mandibulectomy and reconstruction. In this scenario, many surgeons are reluctant to perform a reconstruction with an osseous flap because of the presumed increased morbidity and complexity. The purpose of this study was to evaluate the safety and efficacy of performing a second free fibula flap reconstruction after repeated segmental mandibulectomy.The authors retrospectively reviewed their prospectively maintained departmental database for mandible reconstructions performed between 1991 and 2016, identifying patients who had two sequential free fibula flap reconstructions. Patient, disease, and treatment characteristics were recorded and analyzed.Twenty patients underwent a second free fibula flap reconstruction after a second mandibulectomy. The median follow-up was 72.5 months (range, 16 to 243 months). Preoperative virtual planning was used more often for the second fibula flap compared with the first (50 percent versus 10 percent; p = 0.004). The mean operative times were statistically similar for the first versus second fibula flap (673 minutes versus 586 minutes, respectively; p = 0.13). The postoperative complication rates (50 percent versus 30 percent, respectively; p = 0.19) and functional outcomes were similar between the first and second fibula flap reconstructions.Despite the increased technical complexity, the use of a second free fibula flap after repeated segmental mandibulectomy appears to be safe and to confer no higher risk than that for the first fibula flap.Therapeutic, IV.