In this randomized controlled multicenter trial, we compared endoscopic variceal banding ligation (VBL) with propranolol (PPL) for primary prophylaxis of variceal bleeding. One hundred fifty-two cirrhotic patients with 2 or more esophageal varices (diameter >5 mm) without prior bleeding were randomized to VBL (n ؍ 75) or PPL (n ؍ 77). The groups were well matched with respect to baseline characteristics (age 56 ؎ 10 years, alcoholic etiology 51%, Child-Pugh score 7.2 ؎ 1.8). The mean follow-up was 34 ؎ 19 months. Data were analyzed on an intention-to-treat basis. Neither bleeding incidence nor mortality differed significantly between the 2 groups. Variceal bleeding occurred in 25% of the VBL group and in 29% of the PPL group. The actuarial risks of bleeding after 2 years were 20% (VBL) and 18% (PPL). Fatal bleeding was observed in 12% (VBL) and 10% (PPL). It was associated with the ligation procedure in 2 patients (2.6%). Overall mortality was 45% (VBL) and 43% (PPL) with the 2-year actuarial risks being 28% (VBL) and 22% (PPL). 25% of patients withdrew from PPL treatment, 16% due to side effects. In conclusion, VBL and PPL were similarly effective for primary prophylaxis of variceal bleeding. VBL should be offered to patients who are not candidates for longterm PPL treatment. (HEPATOLOGY 2004;40:65-72.) U pper intestinal hemorrhage is a common and often fatal complication of portal hypertension. It occurs in 30% of patients with cirrhosis, with each bleeding episode bearing a mortality risk of 30% to 50%. 1-3 Thus, prophylactic treatment prior to the first bleeding (i.e., primary prophylaxis) is mandatory in highrisk patients. 4,5 Nonselective -blockers (i.e., propranolol, nadolol)-the current standard prophylaxis-reduce bleeding incidence and bleeding-related mortality. 6 -9 However, pharmacotherapy with -blockers is not optimal: 30% to 40% of patients will not achieve a sufficient reduction of portal pressure to prevent bleeding. 10 -12 Furthermore, contraindications and side effects are common 13,14 and may require withdrawal, which reincreases the risk of bleeding. 15 Therefore, therapeutic alternatives to -blockers are warranted. Due to heterogeneous results, prophylactic endoscopic sclerotherapy is not recommended for the primary prevention of variceal bleeding. 5,7 Compared to injection sclerotherapy, 16 variceal banding ligation (VBL) allows a more rapid and more effective eradication of varices with fewer side effects. 17 To date, only 2 trials comparing VBL with standard treatment (-blockers) have been fully published. 13,18 The results of these studies are controversial and partly inconclusive. In the present article, we report on the results of a prospective randomized multicenter trial comparing propranolol (PPL) and banding ligation for the primary prophylaxis of variceal bleeding in patients with cirrhosis.