Debilitating and complex problems like bile reflux, recurrent aspiration pneumonia, and conduit dysfunction have been observed after esophagectomy with pyloroplasty. The literature is sparse on appropriate patient selection and surgical management of this condition. Our objective was to investigate the selection and outcomes for patients who underwent Roux-en-Y diversion (REYD) for debilitating reflux after esophagectomy. From January 1, 2009, to December 31, 2020, 91 patients underwent Roux-en-Y reconstruction for any cause at Cleveland Clinic Thoracic Surgery service. Seventeen patients received REYD for bile reflux after esophagectomy, of whom 16 had pyloroplasty. Other preoperative symptoms included nausea and vomiting (13, 76%), reflux and regurgitation (11, 65%), and aspiration pneumonia (5,29%). Patient demographics and preoperative, operative, and postoperative details were extracted from prospective quality registries and abstracted from medical records. The Esophageal AbnormaliTy Questionnaire was administered for comprehensive assessment of symptoms. Median time from esophagectomy to REYD was 3.06 years (interquartile range, 1.7-5.7). We observed 77% decrease in nausea and vomiting, 73% decrease in reflux and regurgitation, and 60% decrease in aspiration pneumonia. Postoperative complications included aspiration pneumonia (2, 12%). Nausea, vomiting, and regurgitation were the most common complaints. Serious symptoms such as solid foods getting stuck, regurgitation, dyspepsia, and dumping were rarely reported. Long-term outcomes were remarkable for jejunostomy tube insertion (1, 6%), dilation of anastomotic stricture (1, 6%), and internal and ventral hernia repairs (2, 12%). Median follow-up time was 4.7 years. REYD can provide significant relief from debilitating bile reflux in a selected patient population after medical management is maximized.