A retrospective study was conducted on data of 45 patients who underwent endoscopic submucosal dissection (ESD) at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2013 to March 2024 and were pathologically confirmed as having early esophageal cancer with postoperative defect ≥3/4 of the esophageal circumference, to evaluate the preventive effect of polyglycolic acid sheet (PGA) combined with oral glucocorticoid for esophageal stenosis after ESD of large early esophageal cancer. Patients were divided into two groups according to teatment: oral glucocorticoid alone group ( n=27) and PGA combined with oral glucocorticoid group ( n=18). The results showed that the postoperative esophageal stenosis rate was significantly lower in the PGA combined with oral glucocorticoid group compared with the oral glucocorticoid alone group [44.4% (8/18) VS 74.1% (20/27), χ2=4.034, P=0.043]. For cases of non-circumferential esophageal defects, only 1 case [9.1% (1/11)] experienced postoperative esophageal stenosis in the PGA combined with oral glucocorticoid group, while 10 cases [62.5% (10/16)] in the oral glucocorticoid alone group. During follow-up, no serious complications related to glucocorticoid use or adverse events related to PGA use were observed. These findings suggest that PGA combined with oral glucocorticoid is safe and effective for preventing esophageal stenosis after ESD for large early esophageal cancer and may be more effective than using only oral glucocorticoid.