ObjectiveWe retrospectively evaluated the efficacy of Gamma Knife radiosurgery (GKS) for recurrent nasopharyngeal carcinoma (NPC) in patients who previously underwent radiotherapy, and analyzed the treatment outcomes over 14 years. MethodsTen patients with recurrent NPC who had previously received radiotherapy underwent stereotactic radiosurgery using a Gamma Knife® (Elekta Inc, Atlanta, GA, USA) between 2005 and 2018. The median target volume was 8.2 cm3 (range, 1.7–17.8), and the median radiation dose to the target was 18 Gy (range, 12–30). The median follow-up period was 18 months (range, 6–76 months). Overall and local failure-free survival rates were determined using the Kaplan-Meier method. ResultsThe NPCs recurred at the primary cancer site in seven patients (70%), as distant brain metastasis in two (20%), and as an extension into brain in one (10%). The recurrent tumors in seven of the 10 patients (70%) were found on the routine follow-up imaging studies. Two patients presented with headache and one with facial pain. Local failure after GKS occurred in five patients (50%) : two of whom died eight and 6 months after GKS, respectively. No adverse radiation effects were noted after GKS. The 1- and 3-year overall survival rates after GKS were 90% and 77%, respectively. The local failure-free survival rates at 6 months, 1 year, and 3 years after GKS were 80%, 48%, and 32%, respectively. The median interval from GKS to local failure was 8 months (range, 6–12). Univariate analysis revealed that using co-registration with positron emission tomography-computed tomography (PET-CT) and magnetic resonance imaging (MRI) was associated with a lower local failure rate of recurrent NPC (p=0.027). ConclusionGKS is an acceptable salvage treatment option for patients with recurrent NPC who previously received radiation therapy. PET-CT and MRI co-registration for dose planning can help achieve local control of recurrent NPC.