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Background: Survival rates after a total gastrectomy with adequate lymphadenectomy are improving, leading to a shift in outcomes of interest from survival to postoperative outcomes and symptoms. In this systematic review, we investigate gastrointestinal symptoms that occur after a gastrectomy in relation to exocrine pancreatic insufficiency and the effect of pancreatic exocrine enzyme supplementation on these symptoms. Methods: Online databases PubMed, Embase, and Cochrane Library were systematically searched in accordance with the PRISMA guidelines. Studies that researched gastrointestinal symptoms, exocrine pancreatic function, and enzyme supplementation were identified and assessed. Results: The search resulted in a total of 1,023 articles after exclusion of duplicates. After performing a thorough assessment, 4 studies were included for systematic review. Exocrine pancreatic insufficiency was investigated by 2 studies; the results showed a significant decrease of total exocrine pancreatic function of up to 76%. The other 2 studies investigated the effect of pancreatic enzyme supplementation and found minor improvement in fecal consistency and a decrease in high-degree steatorrhea. No differences in individual symptom scores were reported. Conclusion: Gastrointestinal symptoms such as steatorrhea, bloating, and dumping syndrome may be related to exocrine pancreatic function, initiated by total gastrectomy. Treatment with pancreatic enzymes had a minor positive effect on patients. It should be noted that these studies were of a small sample size and low quality. New and larger RCTs are necessary to either prove or disprove the benefit of pancreatic enzyme replacement therapy in the treatment of the gastrointestinal symptoms after total gastrectomy.