The aim of this study was to investigate the impact of orthotopic liver transplantation (OLT) on plasma levels and splanchnic turnover of key amino acids for muscular (branched-chain amino acids: BCAAs) and hepatic metabolism (aromatic amino acids (AAAs) and methionine) in 48 patients with cirrhosis, 14 patients after OLT, and 46 controls. Also, hepatic amino-acid supply and resting energy expenditure were measured. BCAA levels (no hepatic uptake) decreased in cirrhosis (P<0.001) and were improved, although not normalized, after OLT (P<0.001). AAA and methionine levels were raised in cirrhosis (P<0.001) and normalized after OLT (P<0.001). Hepatic supply of these amino acids increased in patients graded Child B and C and decreased significantly after OLT. Splanchnic uptake of AAAs and methionine increased significantly in Child-B and decreased in Child-C patients. After OLT, splanchnic extraction of AAAs and methionine was as in Child A. Circulating AAAs and methionine correlated with indocyanine-green half-life (r=0.71, P<0.001) and resting energy expenditure (r=0.50, P<0.001), indicating that levels of circulating AAAs and methionine in cirrhosis are determined by hepatic and extra-hepatic metabolic factors. This study demonstrates persistent changes in muscular metabolism of BCAAs after OLT, while the hepatic amino-acid metabolism is normalized due to (1) a significant reduction in the rate of peripheral proteolysis, and (2) improved liver function compared with that in patients with cirrhosis.