Objective To study the efficacy of variceal ligation combined with sclerotherapy and tissue glue injection in the treatment of esophageal and gastric varices. Methods A retrospective analysis was performed on 120 patients with esophageal and gastric varices in our hospital from July 2018 to July 2020. Among them, 67 patients underwent ligationsclerosing agent combined with tissue glue injection and were included in observation group. 53 patients underwent ligation combined with tissue glue injection and were included in control group. The clinical efficacy, endoscopic features (redcolor sign, portal hypertensive gastropathy) at 6 months after surgery, the diameter of varicose veins and portal blood flow velocities (portal vein, left gastric vein, splenic vein) before surgery and at 6 months after surgery and incidence rates of complications were compared between the two groups. Results At 6 months after surgery, the total effective rate of treatment in observation group was higher than that in control group (P＜0.05). The detection rate of redcolor sign under endoscopy in observation group was lower than that in control group (P＜0.05), and there was no statistically significant difference in detection rate of portal hypertensive gastropathy between the two groups (P＞0.05). The diameter of varicose veins in the two groups was smaller than that before surgery, and the diameter in observation group was smaller than that in control group (P＜0.05). The blood flow velocities of portal vein and splenic vein in the two groups were higher than those before surgery, and the velocities in observation group were larger than those in control group (P＜0.05), and the blood flow velocity of the left gastric vein was not statistically different from that before surgery (P＞0.05). There were no statistically significant differences in complications between the two groups (P＞0.05). Conclusion Esophageal and gastric varices ligationsclerosing agent combined with tissue glue injection has an exact efficacy in the treatment of esophageal and gastric varices, and it is helpful to improve the hemodynamic indexes of the portal vein, with mild complications and high safety.