Objective The aim of this study was to compare the long-term local control, overall survival, and late toxicities of positron emission tomography/computed tomography(PET/CT)-guided dose escalation radiotherapy versus conventional radiotherapy in the concurrent chemoradiotherapy treatment of locally advanced nasopharyngeal carcinoma(NPC).Methods A total of 48 patients with stage III–IVa NPC were recruited and randomly administered PET/CTguided dose escalation chemoradiotherapy(group A) or conventional chemoradiotherapy(group B). The dose-escalation radiotherapy was performed using the simultaneous modulated accelerated radiotherapy technique at prescribed doses of 77 gray(Gy) in 32 fractions(f) to the gross target volume(GTV): planning target volume(PTV) 1 received 64 Gy/32 f, while PTV2 received 54.4 Gy/32 f. Patients in group B received uniform-dose intensity-modulated radiotherapy, PTV1 received 70 Gy/35 f and PTV2 received 58 Gy/29 f. Concurrent chemotherapy consisted of cisplatin [20 mg/m2 intravenous(IV) on days 1–4] and docetaxel(75 mg/m2 IV on days 1 and 8) administered during treatment weeks 1 and 4. All patients received 2–4 cycles of adjuvant chemotherapy of the same dose and drug regimen.Results The use of fluorine-18-fluorodeoxyglucose(^(18)F-FDG) PET/CT significantly reduced the treatment volume delineation of the GTV in 83.3%(20/24) of patients. The 5-year local recurrence-free survival rates of the two groups were 100% and 79.2%, respectively(P = 0.019). The 5-year disease free survival(DFS) rates were 95.8% and 75.0%, respectively(P = 0.018). The 5-year local progression-free survival and DFS rates were significantly different. The 5-year overall survival(OS) rates were 95.8% and 79.2%, respectively. Differences in OS improvement were insignificant(P = 0.079). Late toxicities were similar in the two groups. The most common late toxicities of the two arms were grade 1–2 skin dystrophy, xerostomia, subcutaneous fibrosis, and hearing loss. There were no cases of grade 4 late toxicity.Conclusi