BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) is a pivotal technique for excision of early-stage esophageal tumors. However, its primary complication, postoperative esophageal stricture, is a significant challenge owing to the absence of effective preventive measures. Adipose-derived stem cells (ADSCs) have emerged as a promising treatment modality to address this concern. In this study, we aimed to investigate, for the first time, the efficacy of allogenic ADSC injections in preventing esophageal stenosis after ESD. METHODS: We administered allogeneic ADSC injections (same-species but different individual) to a porcine model of ESD as a way to observe the role of ADSC in preventing esophageal stricture. We also co-cultured rats' ADSCs with rats' esophageal fibroblasts and esophageal mucosal epithelial cells to investigate the mechanism. RESULTS: ADSCs notably facilitated epithelial-mesenchymal transition of epithelial cells. Furthermore, ADSC-conditioned medium exhibited a substantial inhibitory effect on fibroblast proliferation and migration, which was mediated by the transforming growth factor-beta pathway. CONCLUSIONS: Our findings underscore the potential of ADSC injections as a promising therapeutic intervention to enhance recovery and prevent post-ESD complications.