PURPOSE: To assess the impact of liver model complexity on the estimated radiation dose to circulating blood during radiation therapy. METHODS AND MATERIALS: Six patients with hepatocellular carcinoma (HCC) were selected covering a range of clinical treatment volume (CTV) sizes and locations. Photon and proton treatment plans were generated for each patient. Planning computed tomography, CTV contours, and dose distributions were deformably registered to the reference livers provided by the International Commission on Radiological Protection report. Three vasculature models were considered: (1) main vascular tree (MVT), (2) coarse vascular tree (CVT) of 1045 vessels, and (3) detailed vascular tree (DVT) of 2041 vessels. Blood dose-volume histograms (bDVH RESULTS: For the 3 lesions located in the left lobe, the estimated μ CONCLUSION: Our study revealed that the impact of liver vasculature model complexity on the estimated dose to blood depended on lesion-specific characteristics. For lesions with larger CTV size on the right liver lobe treated with photons, modeling only major vessels could generate bDVHs that are dosimetrically comparable with bDVHs of more complex vascular models. Increased tumor v