BackgroundAfter esophagectomy for esophageal and esophagogastric cancer, more than half of patients have lost > 10% of their body weight at 12 months. In most cases, the gastric remnant is used for reconstruction after esophagectomy. One of the most serious nutritional complications of this technique is delayed gastric emptying caused by gastric remnant mobilization and denervation of the vagus nerve. The aim of the PYloroplasty versus No Intervention in GAstric REmnant REconstruction after Oesophagectomy (PYNI-GAREREO) trial is to analyze the clinical outcome of modified Horsley pyloroplasty (mH-P) as a method of preventing delayed gastric emptying.MethodsThe PYNI-GAREREO trial is designed as an open randomized, single-center superiority trial. Patients will be randomly allocated to undergo gastric remnant reconstruction with mH-P (intervention group) or no intervention (control group) in parallel groups. All patients with esophageal cancer or esophagogastric cancer planning to undergo curative minimally invasive esophagectomy will be considered for inclusion. A total of 140 patients will be included in the study and randomized between the groups in a 1:1 ratio. The primary outcome is the body weight change at 6 months postoperatively, and the secondary outcomes are the nutritional status, postoperative complications, functional outcome, and quality of life until 1 year postoperatively.DiscussionWe hypothesize that mH-P after minimally invasive esophagectomy more effectively maintains patients’ nutritional status than no pyloroplasty.Trial registrationUMIN Clinical Trials Registry UMIN000045104. Registered on 25 August 2021.https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000051346.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13063-023-07435-5.