Objective To study the short-term (≤3 months) efficacy and safety of esophageal triamcinolone acetonide filling combined with short-course oral methylprednisolone for the prevention of esophageal stenosis after large-area endoscopic submucosal dissection (ESD) (≥3/4 circumference). Methods A total of 14 patients with 15 early esophageal lesions who received ESD after evaluation from June 2021 to September 2022 in Jiangsu Province Hospital of Chinese Medicine were enrolled. All received regular esophageal triamcinolone acetonide filling combined with oral methylprednisolone for 7 weeks until the lesions completely recovered by regenerated squamous epithelium (>95%). Patients with esophageal stricture were treated with additional endoscopic dilatation. The stenosis rate, the interval between the first endoscopic dilation and the completion of ESD, the number of esophageal triamcinolone acetonide filling, the healing time after ESD, and the speed and method of squamous epithelium regeneration were observed. The secondary observations were adverse events such as bleeding and perforation after ESD and adverse events related to steroid hormone. Results No adverse events occurred after ESD in 14 patients. Only 1 patient developed esophageal stenosis, the incidence of stenosis was 7.1% (1/14). The interval between the first dilation and ESD was 39 days. Thirteen patients achieved squamous epithelium regeneration without stenosis or adverse events related to steroid hormone. The median number of esophageal triamcinolone acetonide filling was 6.5 times (4.0-14.0 times), the median healing time was 40 days (32-94 days), and the median healing speed was 0.61 cm²/d (0.30-1.55 cm²/d). Conclusion Esophageal triamcinolone acetonide filling combined with short-course oral methylprednisolone for the prevention of esophageal stenosis after large-area ESD is effective and safe in the short-term follow-up.