Background The current study was performed to investigate whether circulating cell‐free Epstein‐Barr virus DNA (cfEBV DNA) would be useful for posttreatment surveillance in patients with nasopharyngeal carcinoma (NPC). Methods The authors identified a total of 1984 nondisseminated NPC patients from an institutional big‐data research platform. Blood samples were collected within 3 months of the completion of radiotherapy and every 3 to 12 months thereafter for cfEBV DNA analysis. Patients were followed until disease recurrence was detected or for a median of 60 months. Diagnostic performance was assessed by calculating the sensitivity, specificity, and accuracy based on the clinical detection of disease recurrence by conventional surveillance modalities (imaging scans and pathological examination). Results During follow‐up, a total of 767 patients (38.7%) had detectable cfEBV DNA. The recurrence rate among these patients was 63.8% (489 of 767 patients), which was significantly higher than that in patients with undetectable cfEBV DNA (8.6%; 105 of 1217 patients). cfEBV DNA sensitivity, specificity, and accuracy were 68.8%, 80.0%, and 78.2%, respectively, for local recurrence; 80.2%, 80.0%, and 85.9%, respectively, for regional recurrence; and 91.1%, 80.0%, and 92.8%, respectively, for distant metastasis. cfEBV DNA was found to have higher sensitivity for the detection of extrapulmonary metastases (94.9%‐96.5%) compared with pulmonary metastases (78.4%). It is interesting to note that among the patients with disease recurrence with detectable cfEBV DNA, positive cfEBV DNA results preceded radiological and/or clinical evidence of disease recurrence by a median of 2.3 months (interquartile range, 0.1‐9.5 months). In addition, of the 278 cfEBV DNA‐positive patients who did not develop disease recurrence, 227 (81.7%) had transiently positive cfEBV DNA that fell to undetectable levels during long‐term monitoring. Conclusions Plasma cfEBV DNA in patients with NPC appears to be an early sign of tumor recurrence, especially extrapulmonary metastases. Circulating cell‐free Epstein‐Barr virus (EBV) DNA levels in the plasma can be useful for detecting tumor recurrence early after treatment in patients with nasopharyngeal carcinoma, particularly those with extrapulmonary metastases. Positive circulating cell‐free EBV DNA can be detected at a median of 2.3 months before radiological or clinical evidence of disease recurrence is noted.