Objective To evaluate the regular endoscopic therapy for esophageal and gastric variceal bleeding (EGVB) in patients with liver cirrhosis. Methods A total of 305 patients of EGVB with liver cirrhosis who received endoscopic hemostasis in Nanjing Drum Tower Hospital between January 2015 and January 2018 were included in the retrospective cohort study. Patients were divided into the regular endoscopic treatment group (n=145) and the irregular endoscopic treatment group (n=160). The primary outcome measure was rebleeding rate, and the secondary outcome measures were follow-up time, rebleeding interval and rebleeding mortality. Results There were no significant differences between the two groups in terms of gender composition, average age, etiology composition, the cause of disease under or out of control, liver reserve function, or administration of non-selective β-blockers (P>0.05), and the baseline data were comparable. The rebleeding rate was 11.7% (17/145) in the regular endoscopic treatment group and 41.9% (67/160) in the irregular endoscopic treatment group (χ2=38.74, P<0.001). The follow-up time, rebleeding intervals and mortalies of rebleeding in the regular endoscopic treatment group and the irregular endoscopic treatment group were 28.14±11.11 months and 21.10±12.37 months (t=5.21, P<0.001), 12.0 (6.0, 23.0) months and 1.0 (1.0, 6.0) months (U=164.00, P<0.001), and 1.4% (2/145) and 10.6% (17/160) (χ2=11.13, P=0.001), respectively. Conclusion Compared with irregular endoscopic treatment, regular endoscopic treatment of EGVB in patients with liver cirrhosis has more clinical significance, which can significantly reduce the rebleeding rate, prolong the rebleeding interval, and reduce the mortality of rebleeding.