Background Compared with the conventional work‐up (CWU) including computed tomography (CT) of the chest and abdomen, MRI of the head and neck, and skeletal scintigraphy, positron emission tomography (PET)/MRI might improve diagnostic accuracy, shorten the work‐up time, and reduce false‐positive (FP) findings in patients with nasopharyngeal carcinoma (NPC). However, evidence of cost‐effectiveness is needed for the adoption of PET/MRI for the initial staging in NPC. Purpose To evaluate the cost‐effectiveness and clinical value of PET/MRI as an initial staging procedure for NPC. Study Type Retrospective cohort cost effectiveness study. Subjects Three hundred forty‐three patients with a median age of 51 (13–81) years underwent PET/MRI before treatment (the PET/MRI group) and the remaining 677 patients with a median age of 55 (15–95) years only underwent CWU (the CWU group). There were 80 (23.3%) females and 193 (28.5%) females in the PET/MRI and CWU groups, respectively. Field Strength/Sequence 3‐T integrated PET/MRI system, diffusion‐weighted echo‐planar imaging (b = 0 and 1000 s/mm2) and 18F fluorodeoxyglucose PET. Assessment The primary end point was the FP rate. Costs were determined as issued in 2021 by the Medical Insurance Administration Bureau of Zhejiang, China. Statistical Tests Incremental cost effectiveness ratio (ICER) measured cost of using PET/MRI per percent of patients who avoided a FP. A P‐value <0.05 was considered statistically significant. Results For the whole group, the de novo metastatic disease rate was 5.2% (53/1020). A total of 187 patients with FP results were observed. Significantly more patients with FP results were observed in the CWU group compared to the PET/MRI group (25.6% vs. 4.1%). The ICER was $54 for each percent of patients avoiding a FP finding. Data Conclusion Compared with CWU, PET/MRI may reduce the FP risk. Furthermore, PET/MRI may be cost‐effective as an initial staging procedure for NPC. Evidence Level 3 Technical Efficacy Stage 6