Objectives Assessment of viable tumor residue after definitive radiotherapy is essential in patients with nasopharyngeal carcinoma (NPC). This study aimed to investigate the use of Hopkins criteria on positron emission tomography/computed tomography (PET/CT) for posttreatment response evaluation and whether plasma Epstein‐Barr virus (EBV) DNA could bring additional value. Materials and methods NPC patients who underwent FDG‐PET/CT scan within 26 weeks after definitive radiotherapy were retrospectively reviewed. Residual disease was evaluated by Hopkins 5‐point score. Accuracy of Hopkins criteria before and after incorporating EBV DNA was calculated. Prognostic value for locoregional failure‐free survival (LRFFS) and disease‐free survival (DFS) was analyzed. Results One hundred and sixteen patients were evaluated. Median follow‐up time was 28.3 months (range 3.3‐92.0 months). Residual disease was found in 19 (16.4%) patients. Overall, Hopkins criteria had high specificity (86.6%; 95% CI, 78.2%‐92.7%) and negative prognostic value (NPV) (94.4%; 95% CI, 88.7%‐97.3%), while sensitivity and positive prognostic value (PPV) was 73.7% (95% CI, 48.8%‐90.9%), 51.9% (95% CI, 37.8%‐65.6%), respectively. Posttreatment plasma EBV DNA was not predictive of residual tumor (P = .272). PPV and accuracy were 50.0% (95% CI, 32.1%‐67.9%) and 83.0% (95% CI, 73.8%‐90.0%) after incorporating detectable EBV DNA into the scoring system. Positive PET/CT results were significantly correlated with inferior 3‐year LRFFS (95.7% vs 79.5%, P = .043) and 3‐year DFS (84.6% vs 54.4%, P = .028). Conclusions The Hopkins criteria demonstrated high NPV and specificity in posttreatment assessment, with the potential to be a reliable prognostic indicator for locoregional failure. Combining EBV DNA with PET/CT did not improve diagnostic accuracies. PET/CT should not be performed less than 12 weeks after treatment.