Objective To investigate the safety and efficacy of endoscopic varices ligation(EVL) plus endoscopic varices sclerotherapy(EVS)for esophageal varices hemorrhage in patients with liver cirrhosis. Methods Fifty?two liver cirrhosis patients with esophageal varices bleeding were randomly divided into EVL group(n=24)and EVLS group(n=28)according to random numbers generated by computer after first EVL. The EVL group continued undergoing EVL, and the EVLS group was treated by EVS. The interval of treatment was 2 weeks till varices disappeared. All patients were followed up for 18 months with endoscopy and endoscopic ultrasonography(EUS). The efficacy,changes of esophageal varices and perforating veins, varices recurrence and rebleeding were observed. Results There was no significant difference of complete cure rate between EVLS group and EVL group[67.9%(19/28)VS 62.5%(15/24),P>0.05]. The mean session of treatment(2.68±1.0 VS 1.83±0.7,P<0.05), and perforating veins obliteration rate after treatment in EVLS group was higher than that in EVL group[70.8%(17/24)VS 23.8%(5/21),P<0.05]. During 18 months of follow?up,there was no significant difference of rebleeding rate between the two groups[3.6%(1/28)VS 12.5%(3/24),P>0.05],and the varices recurrence rate was higher in EVL group than that in EVLS group[77.3%(17/22)VS 44.0%(11/25), P<0.05]. Child?Pugh class B patients in EVL group had a higher varices recurrence rate compared to that in EVLS group[75.0%(9/12)VS 31.5%(5/16), P<0.05]. Endoscopic recurrences occurred in patients with non?occlusive perforating veins. Conclusion EVL plus EVS sequential procedure is safe and effective for treatment of esophageal varices hemorrhage,especially for Child?Pugh class B patients.Perforating veins may play a key role in the development of esophageal varices and recurrence after endoscopic therapy. EUS findings can direct the endoscopic therapy and predict the variceal recurrence.