BACKGROUND AND AIMS: Esophageal stricture is a severe adverse event after wide-field endoscopic submucosal dissection (ESD) of superficial esophageal carcinoma. This study evaluated the efficacy and safety of combining endoscopic vacuum therapy (EVT) and a budesonide orodispersible tablet (BOT) in preventing post-ESD strictures. METHODS: This prospective case series included patients with superficial esophageal squamous cell carcinoma and adenocarcinoma who had wide-field ESD (≥75% circumference, resection length ≥50 mm). After ESD, EVT was applied immediately followed by 8 weeks of BOTs. The main outcome measurement was the incidence of post-ESD stricture. RESULTS: Eleven patients underwent ESD. Of these, 81.8% had 75% to 99% circumference resected and 18.2% had a circumferential resection. EVT remained in situ for a mean of 3.5 days. No esophageal strictures were observed by the final follow-up, and no major adverse events occurred related to EVT or the BOT. CONCLUSIONS: The prophylactic combination of EVT and BOT is a novel and promising strategy for reducing post-ESD strictures.