Hypofractionated liver stereotactic radiotherapy has produced long-term survival, but the hepatobiliary system is radiosensitive and may be severely damaged by the treatment. We have evaluated long-term radiation effects on hepatobiliary functions in the first long-term survivors reported after radiotherapy to the hepatobiliary system for liver tumors. Eleven patients were followed for up to 13 years after treatment of tumors≤9 cm in size. Conventional blood chemistry, clearance of indocyanine green and segmental uptake and excretion of radiolabeled mebrofenin were assayed. Slightly abnormal routine blood chemistry was found during the first 2 years in some patients with pre-existing liver damage. Other parameters were seemingly unaffected, and liver segments which received differing mean doses did not differ measurably with regard to parenchymal or ductal function. Late liver functions were therefore not demonstrably affected by the radiotherapy in most patients even in the presence of mild cirrhosis, after previous exposure to liver toxic agents, or after resection. However, slight to moderate late dysfunction occurred in one patient after three courses of irradiation, and in a cirrhotic patient after two major liver resections following radiotherapy. Our previous doses for irradiation of liver tumors gave no measurable chronic side effects and may be increased in order to control tumors more effectively. In selected patients, irradiation is possible even in the presence of liver dysfunction, and previous irradiation or resection does not absolutely contraindicate salvage treatment by re-irradiation or resection.