Endoscopic variceal ligation therapy (EVL) seems to be a more effective and safer method than endoscopic injection variceal sclerotherapy (EVS) for treating bleeding esophageal varices. However, EVL may entail a higher recurrence rate than EVS. The aim of this study was to examine whether EVL combined with low-dose EVS reduced the recurrence rate compared to treatment with EVL alone and reduced the complication rate compared to treatment with EVS alone. In this prospective study, 59 patients with cirrhosis and high-risk (F2 or F3, red color sign ++ or +++) esophageal varices were enrolled. They were randomly assigned to an EVS group (n = 18), an EVL group (n = 20), and a combination EVL plus low-dose EVS group (n = 21). After the eradication of varices, follow-up endoscopic examinations were carried out for 24 months to determine the recurrence of varices. Complications, e.g., severe dysphagia, fever, renal dysfunction and pleuritis were also evaluated. The recurrence-free rate was significantly lower in the EVL group (60% at 24 months) than in either the EVS group (90%, P < 0.05) or the combination group (88%, P < 0.05). However, no significant difference was found between the EVS group and the combination group. The complication rate was significantly higher in the EVS group (50%) than in either the EVL group (5%, P < 0.01) or the combination group (10%, P < 0.01). The combination therapy seems to be useful to improve the benefits achieved with EVL alone and to reduce the harmful effects induced by EVS alone. EVL plus low-volume EVS is advisable in the treatment of high-risk esophageal varices.