Without liver transplantation, survival averages 7–10 years once symptoms develop but has improved for younger women since the introduction of ursodeoxycholic acid. Progression to liver failure and portal hypertension is associated with the presence of anti-gp210 and anticentromere antibodies, respectively, and may be accelerated by smoking. Patients with early-stage disease in whom the alkaline phosphatase and AST are less than 1.5 times normal and bilirubin is 1 mg/dL (17.1 mcmol/L) or less after 1 year of therapy with ursodeoxycholic acid (Paris II criteria) are at low long-term risk for cirrhosis and have a life expectancy similar to that of the healthy population. Pregnancy is well tolerated in younger patients. In advanced disease, an adverse prognosis is indicated by a high Mayo risk score that includes older age, high serum bilirubin, edema, low serum albumin, and prolonged prothrombin time as well as by variceal hemorrhage. Other prognostic models include the Globe index, which is based on age, serum bilirubin, serum albumin, serum alkaline phosphatase, and platelet count and, in treated patients, the UK-PBC score, which is based on the baseline serum albumin and platelet count and the serum bilirubin, aminotransferases, and alkaline phosphatase after 12 months of ursodeoxycholic acid. An increase in liver stiffness of more than 2.1 kilopascals per year indicates an adverse prognosis. A prediction tool for varices has been proposed based on the serum albumin, serum alkaline phosphatase, platelet count, and splenomegaly. Liver transplantation should be considered when the MELD-Na score is at least 15, total serum bilirubin at least 6, or Mayo risk score at least 7.8. Fatigue is associated with an increased risk of cardiac mortality and may not be reversed by liver transplantation. Among asymptomatic patients, at least one-third will become symptomatic within 15 years. The risk of hepatocellular carcinoma appears to be increased in patients with PBC; risk factors include older age, male sex, prior blood transfusions, advanced histologic stage, signs of cirrhosis or portal hypertension, and a biochemical nonresponse to ursodeoxycholic acid. Liver transplantation for advanced PBC is associated with a 1-year survival rate of 85–90%. The disease recurs in the graft in 20% of patients by 3 years, but this does not seem to affect survival.