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Background: To explore the short‐ and long‐term outcomes in patients with nasopharyngeal carcinoma (NPC) with magnetic resonance imaging (MRI)‐detected residual disease at 3 months post‐treatment who received intervention either promptly (0 month) or following observation (after an additional 3 months). Methods: A total of 272 patients with residual disease at 3 months post‐treatment (observation [observation for additional 3 months]: 122, intervention [prompt intervention]: 150) were analyzed. Univariate and multivariate analyses were performed to examine the survival. Adverse events were analyzed in all patients. Results: Patients in the observation group had a lower 3‐year overall survival (77.1% vs. 85.2%), progression‐free survival (10.2% vs. 18.1%), and locoregional relapse‐free survival (10.2% vs. 20.6%) (all p <.05), but not distant metastasis‐free survival (83.8% vs. 78.4%, p =.189), whereas patients in the intervention group achieved higher complete remission (CR) rates (43.3% vs. 21.2%, p =.003). Patients who achieved CR after prompt intervention had a better survival rate than those who achieved observation‐CR or non‐CR (p <.001). Multivariate analyses revealed that a wait‐and‐see policy was an independent prognostic factor for impaired survival (p <.001). No significant differences of acute or late toxicities were observed between the two groups. Conclusions: Patients with NPC with MRI‐detected residual disease 3 months post‐radiotherapy should be encouraged to undergo prompt intervention rather than adopting a passive wait‐and‐see policy. [ABSTRACT FROM AUTHOR]