Background: This study was performed to investigate whether long-term monitoring of dynamic changes in plasma Epstein-Barr virus (EBV) DNA could improve prognosis prediction of nasopharyngeal carcinoma (NPC).Methods: 1077 non-metastatic NPC patients were recruited to retrospectively analyze the prognostic value of plasma EBV DNA load pre-treatment and 3, 12, 24, and 36 months post-treatment. We also examined the prognostic value of dynamic changes in plasma EBV DNA at various time points.Results: Patients with plasma EBV DNA load above optimal pre- and post-treatment cut-offs had significantly worse five-year progression-free survival, distant metastasis-free survival, locoregional relapse-free survival, and overall survival(OS) at all time points, excluding only OS at 36 months post-treatment due to limited mortalities. Patients with persistently undetectable plasma EBV DNA at the first four time points had the best prognosis, followed by those with positive detection pre-treatment and consistently negative detection post-treatment, those with negative detection pre-treatment and positive detection at one time point post-treatment, and those with positive detection pre-treatment and at one time point post-treatment, whereas patients with positive detection at ≥2 time points post-treatment had the worst prognosis. Cox proportional hazard models identified the dynamic change pattern as an independent prognostic factor, and ROC curve analysis demonstrated that the dynamic change at four time point was more valuable than any single time point for predicting disease progression, distant metastasis, locoregional relapse, and mortality.Conclusions: Dynamic changes in plasma EBV DNA pre- and post-treatment could predict the long-term survival outcome and provide accurate risk stratification in NPC.