BackgroundPostoperative stricture and refractory stricture are severe adverse events which occur after expansive esophageal endoscopic submucosal dissection (ESD). The aim of this study was to assess the efficacy of steroid injection, polyglycolic acid (PGA) shielding, and of additional steroid injection thereafter for the prevention of refractory esophageal stricture.MethodsThis is a retrospective cohort study of 816 consecutive cases of esophageal ESD performed between 2002 and 2021 at the University of Tokyo Hospital. After 2013, all patients with a diagnosis of superficial esophageal carcinoma covering over 1/2 the esophageal circumference underwent preventive treatment immediately after ESD with either “PGA shielding”, “steroid injection”, or “steroid injection + PGA shielding”. Additional steroid injection was performed for high-risk patients after 2019.ResultsThe risk of refractory stricture was especially high in the cervical esophagus (OR 24.77,p= 0.002) and after total circumferential resection (OR 894.04,p< 0.001). “Steroid injection + PGA shielding” was the only method significantly effective in preventing stricture occurrence (OR 0.36; 95% CI 0.15–0.83,p= 0.012). This method also decreased the risk of refractory stricture (OR 0.38; 95% CI 0.10–1.28,p= 0.096), but additional steroid injection was the only significantly effective method for prevention of refractory stricture (OR 0.42; 95% CI 0.14–0.98,p= 0.029).ConclusionCombining steroid injection and PGA shielding is effective for preventing post-ESD stricture and refractory stricture. Additional steroid injection is a viable option for patients at high-risk for refractory stricture.Graphical abstractSupplementary InformationThe online version contains supplementary material available at 10.1007/s00464-023-10111-z.