OBJECTIVE Combining endoscopic sclerotherapy with ligation has been proposed to hasten variceal eradication. A randomized trial was performed comparing combination ligation plus sclerotherapy with ligation alone in patients with major bleeding from esophageal varices. METHODS Forty-one patients were randomly assigned to receive ligation or ligation plus 1 mL 1.5% tetradecyl injected just above each band. Treatment was repeated weekly until varices were eradicated. Repeat endoscopy was performed for rebleeding and every 3 months after eradication. RESULTS No significant differences were found between combined therapy and ligation in rebleeding (29% vs. 30%), blood transfused (3.1 +/- 1.1 vs. 2.0 +/- 0.8 U), hospital days (9.3 +/- 2.1 vs. 7.5 +/- 1.2), complications (29% vs. 10%), or deaths (14% vs. 15%) during a mean follow-up period of 28 weeks. Combined therapy required significantly more sessions to achieve eradication (4.9 +/- 0.6 vs. 2.7 +/- 0.4) and greater time per treatment session (18.3 +/- 1.7 vs. 13.3 +/- 0.5 minutes). CONCLUSIONS Combined ligation plus sclerotherapy does not reduce the number of treatment sessions required for variceal eradication as compared with ligation alone. Combined therapy lengthens the time required for treatment without improving efficacy or decreasing complications. Thus, combined ligation and sclerotherapy should not be used to treat patients with bleeding esophageal varices.