INTRODUCTION: Major hepatopancreatobiliary surgery is associated with a risk of major blood loss. The authors aimed to assess whether autologous transfusion of blood salvaged intraoperatively reduces the requirement for postoperative allogenic transfusion in this patient cohort. MATERIALS AND METHODS: In this single centre study, information from a prospective database of 501 patients undergoing major hepatopancreatobiliary resection (2015-2022) was analysed. Patients who received cell salvage ( n =264) were compared with those who did not ( n =237). Nonautologous (allogenic) transfusion was assessed from the time of surgery to 5 days postsurgery, and blood loss tolerance was calculated using the Lemmens-Bernstein-Brodosky formula. Multivariate analysis was used to identify factors associated with allogenic blood transfusion avoidance. RESULTS: 32% of the lost blood volume was replaced through autologous transfusion in patients receiving cell salvage. Although the cell salvage group experienced significantly higher intraoperative blood loss compared with the noncell salvage group (1360 ml vs. 971 ml, P =0.0005), they received significantly less allogenic red blood cell units (1.5 vs. 0.92 units/patient, P =0.03). Correction of blood loss tolerance in patients who underwent cell salvage was independently associated with avoidance of allogenic transfusion (Odds ratio 0.05 (0.006-0.38) P =0.005). In a subgroup analysis, cell salvage use was associated with a significant reduction in 30-day mortality in patients undergoing major hepatectomy (6 vs. 1%, P =0.04). CONCLUSION: Cell salvage use was associated with a reduction in allogenic blood transfusion and a reduction in 30-day mortality in patients undergoing major hepatectomy. Prospective trials are warranted to understand whether the use of cell salvage should be routinely utilised for major hepatectomy.