Over a 9-year period, major resection was successfully performed on 51 occasions with total vascular exclusion using supra- and infrahepatic caval and portal vein clamping. The main indications for hepatic resection were centrally located tumor in liver metastases (62%) and hepatocellular carcinoma with no evidence of co-existing cirrhosis (25%). Major resections included extended and regular right hepatectomy, extended left hepatectomy, and segmentectomy. The mean duration of vascular exclusion was 46.5 +/- 5.0 minutes (range 20 to 70 minutes) and mean blood transfusion requirement was 1.4 +/- 0.4 units during vascular exclusion. There were significant correlations between postoperative fall in factor II levels and the number of segments removed (r = 0.37, p = 0.015) and between serum alanine aminotransferase levels at day 2 and the duration of vascular exclusion (r = 0.35, p = 0.02). One patient died 45 days after the procedure of multi-organ failure and sepsis. Nonfatal complications occurred in 7 patients (14%) and included respiratory infection (7 patients), biliary fistula (3 patients), and collection at the site of hepatic resection (3 patients). Total vascular exclusion is a safe and useful technique in resection of major hepatic lesions that involve hepatic veins.