Objective To evaluate balloon compression-assisted endoscopic injection sclerotherapy (bc-EIS) for the treatment of esophageal varices. Methods From June 2019 to November 2020, cirrhotic patients with esophageal varices who received endoscopic injection sclerotherapy (EIS) in the First Affiliated Hospital of Anhui Medical University were enrolled in the study. The patients were randomly divided into the bc-EIS group and the traditional EIS group. The number of treatments to eradicate varicose veins, the dose of sclerosing agent used in the first treatment, the number of injection points in the first treatment, the rebleeding rate within 10 months after the operation and the incidence of complications or adverse reactions were compared between the two groups. Results Ninety-two cases were initially included in the study, and 7 cases were excluded based on exclusion criteria. Finally, 85 cases were included in the data analysis, 47 in the bc-EIS group and 38 in the traditional EIS group. The first eradication rate, the second cumulative eradication rate and the third cumulative eradication rate were 82.98% (39/47), 91.49% (43/47) and 100.00% (47/47) in the bc-EIS group, and they were 10.53% (4/38) (χ2=44.125, P<0.001), 31.58% (12/38) (χ2=33.023, P<0.001) and 63.16% (24/38) (χ2=20.730, P<0.001), respectively in the traditional EIS group, and the differences were statistically significant. The treatment times of eradicating varicose veins in the bc-EIS group and the traditional EIS group were 1.25±0.60 and 3.21±1.41, respectively, with significant difference. The dosage of sclerosing agent in first treatment in the bc-EIS group and the traditional EIS group was 17.66±7.14 mL and 22.92±6.84 mL, respectively (t=3.441, P=0.001). The numbers of initial injection points in the bc-EIS group and the traditional EIS group were 2.70±0.86 and 2.78±1.04, respectively and the difference was not statistically significant (t=1.847, P=0.065). The rebleeding rates of the two groups within 10 months after the operation were 2.13% (1/47) and 18.42% (7/38) respectively (χ2=4.771, P=0.029). There were no serious complications in the two groups. The incidences of retrosternal pain, nausea and vomiting, abdominal distension and ulcer were 2.13% (1/47), 2.13% (1/47), 4.26% (2/47) and 0.00% (0/47) in the bc-EIS group, and in the traditional EIS group, they were 5.26% (2/38) (χ2=0.035, P=0.851), 5.26% (2/38) (χ2=0.035, P=0.851), 7.89% (3/38) (χ2=0.060, P=0.806) and 7.89% (3/38) (χ2=1.877, P=0.171), respectively, without significant difference. Conclusion Bc-EIS is more effective than traditional EIS for the treatment of esophageal varices with lower postoperative rebleeding rate, which shows better clinical application value.