Abstract Background Surgery remains the mainstay of curative pathway treatment for most patients with esophageal and gastric cancer. Both esophagectomy and gastrectomy carry a significant risk of early post-operative morbidity. The gastrointestinal, nutritional, and endocrine effects of surgery can have a significant impact on patients’ quality of life and include small intestinal bacterial overgrowth, pancreatic exocrine insufficiency, bile acid malabsorption, hypoglycaemia, dumping, and others. Early diagnosis and treatment for these consequences of surgery can significantly improve quality of life. We developed a protocol for the investigation and management of patients with symptoms post-esophagogastric resection and implemented this within a nurse-led follow-up clinic. Methods A multi-disciplinary team was involved in the design of a protocol for the investigation and management of late effects following esophagectomy or gastrectomy. The protocol was implemented within a nurse-led clinic with prospective follow-up of all patients following resection. Following the introduction of the protocol, patients were divided into two groups; those with symptoms undergoing investigation prior to introduction of the protocol and all patients prospectively following introduction of the protocol in October 2022 to December 2023. The prevalence of patients undergoing investigation and the time from documentation of symptoms to diagnosis and the prevalence of each diagnosis were assessed. Results A total of 217 patients were studied, of whom 93 were part of the pre-protocol (symptomatic) group and the remaining 124 were part of the post-protocol prospective group. Within the pre-protocol group, 67 (72.0%) patients underwent investigation for late effects following surgery. The median time between the presentation of symptoms to diagnosis in the pre-protocol group was 7 months. Within the post-protocol prospective group, 33 (26.6%) patients underwent investigation for late effects following surgery. The median time between the presentation of symptoms to diagnosis in the post-protocol group was 2 months, representing a 71.4% reduction compared to the pre-protocol group. Conclusion Gastrointestinal, nutritional, and endocrine effects of esophagectomy and gastrectomy remain common. In symptomatic patients, a protocolised approach to investigation shortened the time to diagnosis and treatment by a median of 5 months. This approach can be successfully employed within a nurse-led follow-up pathway supported by a multidisciplinary team.