Background: The role of salvage endoscopic surgery compared with intensity-modulated radiotherapy (IMRT) in the primary treatment of patients with resectable locally recurrent nasopharyngeal carcinoma (lrNPC) who had received prior radiotherapy is a matter of debate. Methods: In this multicenter, open-label, randomized controlled trial, patients with lrNPC were enrolled from 3 hospitals in southern China. The key inclusion criteria were patients pathologically diagnosed with undifferentiated or differentiated, nonkeratinizing lrNPC with tumors confined to the nasopharyngeal cavity (rT1), the postnaris or nasal septum (rT2a), the superficial parapharyngeal space (rT2b), or the base wall of the sphenoid sinus (rT3) (according to the 6 th edition American Joint Committee on Cancer (AJCC) classification). Eligible patients were randomly assigned in a 1:1 ratio to receive either endoscopic nasopharyngectomy (ENPG) or IMRT. The primary endpoint was overall survival (OS). The secondary endpoints were disease-free survival (DFS), locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), and safety. This trial was prospectively registered at the Chinese Clinical Trial Registry, number ChiCTR-TRC-11001573. Findings: Between September 30, 2011, and January 16, 2017, 200 eligible patients were randomly assigned to receive ENPG (n= 100) or IMRT (n= 100). At a median follow-up of 56.0 (95% confidence interval [CI] 51.4 - 60.6) months, the 3-year OS was 85.8% in the ENPG arm and 68.0% in the IMRT arm (hazard ratio [HR] 0.47; 95% CI, 0.29 to 0.76; P = 0.002). The DFS, LRRFS, and DMFS at 3 years for the ENPG arm and IMRT arm were 76.5% and 56.5% (HR 0.54; 95% CI, 0.36-0.81; P = 0.003), 89.8% and 79.4% (HR 0.49; 95% CI, 0.25-0.96; P = 0.033) and 94.4% and 91.4% (HR 0.87; 95% CI, 0.35-2.20; P = 0.774), respectively. The incidence of grade ≥3 radiation-related adverse events was 13.1% in the ENPG group and 36.6% in the IMRT group. Interpretation: Endoscopic surgery significantly improved OS compared with IMRT in patients with resectable lrNPC. Trial Registration: This trial was prospectively registered at the Chinese Clinical Trial Registry, number ChiCTR-TRC-11001573. Funding Statement: Sun Yat-sen University Clinical Research 5010 Program (2010004), National Natural Science Foundation of China (NSFC) grants (81900918, 81870696, 81670902), Guangdong Natural Science Foundation of China grants (2018B030312008, 2018A030313667), Guangzhou Science and Technology Project of China grant (201704020098, 201605030003), Sun Yat-sen University Young Teacher Cultivation Program (19ykpy68). Declaration of Interests: We declare no competing interests. Ethics Approval Statement: The institutional ethics review board approved the trial protocol. The trial was performed in accordance with the Declaration of Helsinki, and the results are reported according to the CONSORT statement. All participants provided written informed consent.