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Simple Summary: A chest CT via central vein enhancement not only eliminates peripheral vein regurgitation but also provides better image quality that facilitates precise clinical staging. A chest CT via central vein enhancement may be considered after tissue proof in order to better discriminate disease severity. The differences in chest computed tomography (CT) image quality may affect the tumor stage. The aim of this study was to compare the image quality and accuracy of chest CT via central vein and peripheral vein enhancement. Fifty consecutive patients were enrolled from a tertiary medical center in Taiwan from May 2016 to March 2019. All the patients received a chest CT via central vein enhancement prior to neoadjuvant concurrent chemoradiation in order to compare the chest CT that was obtained via the peripheral vein. In addition, blind independent central reviews of chest CT via central vein and peripheral vein enhancement were conducted. For T and N stage, chest CT via central vein enhancement had a greater consistency with endoscopic ultrasonography and positron-emission tomography-computed tomography findings (kappa coefficients 0.4471 and 0.5564, respectively). In addition, chest CT via central vein enhancement also showed excellent agreement in the blind independent central review (kappa coefficient 0.9157). The changes in the T and N stage resulted in stage migration in 16 patients. Chest CT via central vein enhancement eliminated peripheral vein regurgitation and also provided more precise clinical staging. This study is registered under the registered NCT number 02887261. [ABSTRACT FROM AUTHOR]