Ninety-seven patients with recent or active variceal bleeding were randomly assigned to oral propranolol, endoscopic sclerotherapy plus oral propranolol, or transhepatic sclerotherapy plus oral propranolol. The effects of treatment on the number of units transfused, rebleeding of any magnitude, major rebleeding, and death were assessed in these patients, 82% of whom were alcoholic and 81% Child's Class C. After a minimum follow-up interval of 2 yr (range, 27-65 mo), major rebleeding rates were 65% for propranolol alone, 45% for endoscopic sclerotherapy plus propranolol, and 60% for transhepatic sclerotherapy plus propranolol. The corresponding death rates were 81% for propranolol alone, 55% for endoscopic sclerotherapy plus propranolol, and 66% for transhepatic sclerotherapy plus propranolol (p = 0.03). Thirty-three patients (34%) never received propranolol; 8 due to medical contraindications and 25 because they died or bled enough to meet the definition of treatment failure within 3 or 4 days of randomizations (no significant differences among treatment groups). Patients assigned to propranolol alone bled sooner, bled more units, and had a higher mortality rate than patients treated by endoscopic sclerotherapy plus propranolol. Patients treated with transhepatic sclerotherapy plus propranolol had intermediate results. Propranolol alone is inadequate treatment for esophageal variceal bleeding in patients with advanced liver disease.