We conducted a prospective study of 321 patients with cirrhosis of the liver and esophageal varices with no history of bleeding to see whether a comprehensive analysis of their clinical features and of the endoscopic appearances of their varices could help to identify those at highest risk for bleeding. Varices were classified endoscopically as suggested by the Japanese Research Society for Portal Hypertension. Patients were followed for 1 to 38 months (median, 23), during which 85 patients (26.5 percent) bled. Multiple regression analysis (Cox's model) revealed that the risk of bleeding was significantly related to the patient's modified Child class (an index of liver dysfunction based on serum albumin concentration, bilirubin level, prothrombin time, and the presence of ascites and encephalopathy), the size of the varices, and the presence of red wale markings (longitudinal dilated venules resembling whip marks) on the varices. A prognostic index based on these variables was devised that enabled us to identify a subset of patients with a one-year incidence of bleeding exceeding 65 percent. The index was prospective validated on an independent sample of 75 patients with varices and no history of bleeding. We conclude that our prognostic index, which identifies groups of patients with one-year probabilities of bleeding ranging from 6 to 76 percent, can be used to identify candidates for prophylactic treatment.