To compare the effect of endoscopic ligation with that of sclerotherapy in the treatment of patients with bleeding esophageal varices. Strategies to identify published and unpublished research included searches of computerized bibliographic and scientific citations, review of citations in relevant primary articles, searches of services providing information on unpublished studies, contact with primary investigators and the ligation equipment manufacturer, and review of proceedings from pertinent scientific meetings. From 158 potentially relevant articles, duplicate independent review identified 7 relevant randomized trials that compared endoscopic ligation with sclerotherapy for the treatment of patients with bleeding esophageal varices. Independent, duplicate data abstraction of the population, intervention, outcome, and methodologic quality of the trials was done. Ligation therapy compared with sclerotherapy reduced the rebleeding rate (odds ratio, 0.52 [95% CI, 0.37 to 0.74]), the mortality rate (odds ratio, 0.67 [CI, 0.46 to 0.98]), and the rate of death due to bleeding (odds ratio, 0.49 [CI, 0.24 to 0.996]). Four patients would need to be treated with ligation instead of sclerotherapy to avert one rebleeding episode, and 10 would need to be treated with ligation instead of sclerotherapy to prevent one death. Esophageal strictures occurred less frequently with ligation (odds ratio, 0.10 [CI, 0.03 to 0.29]), but no significant differences were seen between treatments for pulmonary infections or bacterial peritonitis. Additionally, the number of endoscopic treatment sessions required to achieve variceal obliteration was lower with ligation than with sclerotherapy. On the basis of lower rates of rebleeding, mortality, and complications and the need for fewer endoscopic treatments, ligation should be considered the endoscopic treatment of choice for patients with esophageal variceal bleeding.