ObjectiveThe purpose of this study was to analyze the dosimetric effect of different isocenters with volumetric modulated arc therapy for nasopharyngeal carcinoma (NPC).MethodsA total of 20 NPC patients who had received radiotherapy were re‐planned by the volumetric modulated arc therapy plan. Three volumetric modulated arc therapy plans with different isocenters were generated for each patient: the first plan using the center of PGTVnx as the isocenter (AP‐V), the second plan using the center of PGTVnd as the isocenter (BP‐V), and the third plan using the center of PTV2 as the isocenter (CP‐V). The conformity and homogeneity indexes of the target, dose‐volume histogram of organs at risk, normal tissue, volume of dose, and monitor units were compared for the three plans.ResultsAP‐V provided a significantly lower maximum dose for the optic nerves and optic chiasm; lower mean dose for the eyeballs; lower absolute volume >10 Gy, absolute volume >20 Gy, and absolute volume >30 Gy; and fewer monitor units than BP‐V and CP‐V. BP‐V and CP‐V provided a significantly lower absolute volume >50 Gy than AP‐V. In the conformity indexes of PGTVnd and PTV2, BP‐V and CP‐V were significantly better than in AP‐V. In the homogeneity index of PTV2, BP‐V and CP‐V were significantly better than in AP‐V. In general, there is no significant difference between BP‐V and CP‐V.ConclusionsAll three plans achieved the clinical demands. AP‐V decreased the volumes of absolute volume >10 Gy, absolute volume >20 Gy, and absolute volume >30 Gy, whereas BP‐V and CP‐V decreased the volume of absolute volume >50 Gy. In terms of organs at risk, AP‐V offered better protection of the optic nerves, optic chiasm, and eyeballs for NPC than BP‐V and CP‐V. Most importantly, AP‐V enhanced the utilization of the monitor units. For this reason, we propose that the radiotherapy technician put the location position in the PGTVnx center during simulation of the NPC patients. We further propose that the isocenter be moved to the geometric center of PGTVnx if the NPC patient plan has higher dosimeter requirements for the optic nerves, optic chiasm, or eyeballs.