Background: Perioperative anemia and red blood cell (RBC) transfusions are common in patients undergoing gastrointestinal cancer surgery. To adequately balance the risks and benefits of transfusion, clinicians must understand the potential effect of transfusions on long-term outcomes. Methodologic issues have limited previous studies exploring the association between RBC transfusion and survival in this specific patient population. Our objective was to determine, among patients who have undergone gastrointestinal cancer resection, if perioperative RBC transfusions are associated with higher risk of all-cause and cancer-specific death. Methods: In this population-based retrospective cohort study, we used administrative datasets containing routinely collected data from Ontario, Canada. Patients who underwent gastrointestinal cancer resection between January 1, 2007 and March 31, 2019 and survived at least 90 days postoperatively were eligible for inclusion. All-cause death from the ninetieth post-operative day was compared between groups using Kaplan-Meier methods and Cox proportional hazards models. Cancer-specific death was compared using competing risk methods. Regression adjusted for potential confounders. Sensitivity analyses, including the E-value, evaluated the robustness of estimates. Results: We identified 74,962 patients (mean age, 67.7 years; 55.4% male; 79.7% colorectal cancer) who underwent resection for gastrointestinal cancer and survived at least 90 days after surgery. Over a median follow-up of 4.1 years (interquartile range 1.9-5.0 years), patients who received RBC transfusions demonstrated increased hazards of all-cause and cancer-specific death relative to patients who were not transfused (hazard ratio: 1.39, 95% confidence interval 1.34 to 1.44; cause-specific hazards ratio: 1.36, 1.30 to 1.43). The adjusted risk of all-cause death was higher in early follow-up intervals (3-6 months post-operatively) but remained elevated in each subsequent interval over 5 years. Conclusions: RBC transfusion among patients with gastrointestinal cancer is associated with increased all-cause death; this persisted over time suggesting a long-term effect of perioperative transfusion. These findings should help clinicians balance the risks and benefits of transfusion and highlight the need for well-designed, multicenter randomized trials to determine if aggressive transfusion avoidance protocols could improve patient survival after gastrointestinal cancer surgery.