Background: Resection of hepatocellular carcinoma is associated with high rates of morbidity and mortality. Since intensive nutritional support can reduce the catabolic response and improve protein synthesis and liver regeneration, we performed a prospective study to investigate whether perioperative nutritional support could improve outcome in patients undergoing hepatectomy for hepatocellular carcinoma. Methods: We studied 124 patients undergoing resection of hepatocellular carcinoma. Sixty-four patients (39 with cirrhosis, 18 with chronic active hepatitis, and 7 with no associated liver disease) were randomly assigned to receive perioperative intravenous nutritional support in addition to their oral diet, and 60 patients (33 with cirrhosis, 12 with chronic active hepatitis, and 15 with no associated liver disease) were randomly assigned to a control group. The perioperative nutritional therapy consisted of a solution enriched with 35 percent branched-chain amino acids, dextrose, and lipid emulsion (50 percent medium-chain triglycerides) given intravenously for 14 days perioperatively. Results: There was a reduction in the overall postoperative morbidity rate in the perioperative-nutrition group as compared with the control group (34 percent vs. 55 percent; relative risk, 0.66; 95 percent confidence interval, 0.45 to 0.96), predominantly because of fewer septic complications (17 percent vs. 37 percent; relative risk, 0.57; 95 percent confidence interval, 0.34 to 0.96). There were also a reduction in the requirement for diuretic agents to control ascites (25 percent vs. 50 percent; relative risk, 0.57; 95 percent confidence interval, 0.37 to 0.87), less weight loss after hepatectomy (median loss, 0 kg vs. 1.4 kg; P = 0.01), and less deterioration of liver function as measured by the change in the rate of clearance of indocyanine green (-2.8 percent vs. -4.8 percent at 20 minutes, P = 0.05). These benefits were seen predominantly in the patients with underlying cirrhosis who underwent major hepatectomy. There were five deaths during hospitalization in the perioperative-nutrition group, and nine in the control group (P not significant). Conclusions: Perioperative nutritional support can reduce complications after major hepatectomy for hepatocellular carcinoma associated with cirrhosis., Resection of hepatocellular carcinoma is associated with high rates of morbidity and mortality¹–³. This is because the majority of patients have cirrhosis, and hepatectomy causes further deterioration of liver function⁴ due to the loss of functioning liver mass. Postoperative sepsis is the other main cause of morbidity and mortality and may be due in part to an enhanced catabolic response to surgery, increased proteolysis, and decreased immunocompetence in patients with cirrhosis who are already hypercatabolic,⁵,⁶ malnourished, and immunocompromised⁷. Since intensive nutritional therapy can reduce the net catabolic response to surgery,⁸ improve protein synthesis (which is critical…