In this study, we developed a system for calculating patient positional displacement between DRs and DRRs, evaluated its practicality for patient data at five lesion sites, and assessed its ROI size dependency at these five sites. We found that almost all prostate, lung, and H&N cancer cases were acceptable for our setup tolerance in clinical practice. Additionally, our comparison of calculation errors for each ROI size suggested the causes of decreased calculation accuracy. In the future, it is necessary to determine how to exclude low‐reproducibility regions from the calculation to improve accuracy in tumors of the liver and pancreas.