BackgroundPatients undergoing pancreatic resection who decline blood transfusion represent a clinical challenge. While bloodless medicine programs are valuable, their impact remains unclear, especially for those with borderline-resectable and locally advanced pancreatic ductal adenocarcinoma (PDAC). MethodsRetrospective review of institutional databases identified patients who did not accept blood transfusion and underwent pancreatic resection from 2013–2022. We collated hemoglobin values, interventions to minimize symptomatic anemia, and patient outcomes. ResultsThirteen patients were identified. Median age was 63 years (range: 52–75 years) and eight (61.5 %) were female. All procedures were performed electively for invasive malignancy with PDAC as the most common diagnosis (11/13; 84.6 %) and pancreaticoduodenectomy as the most common procedure (11/13; 84.6 %). Vascular involvement was common in the 11 patients with PDAC (borderline-resectable: 7/11; 63.6 % and locally advanced: 3/11; 27.3 %), as was the use of multi-agent chemotherapy (n = 10) and preoperative radiotherapy (n = 8) prior to surgery. Median blood loss was 400 mL (range: 100–2200 mL). Intraoperative measures included acute normovolemic hemodilution in one patient and red blood cell salvage in three patients. Median preoperative hemoglobin was 12.3 g/dL (range: 10.3–14.2 g/dL) and median nadir hemoglobin was 9.2 g/dL (range: 5.2–11.8 g/dL). Median hospital stay was 10 days (range: 6–42 days). Thirty-day mortality was 0 % and one-year overall survival was 69.2 % with median follow-up of 26.4 months. ConclusionPancreatic resections can be performed safely in patients who decline blood transfusion, even with borderline-resectable and locally advanced PDAC. Avoiding transfusions and employing blood-conservation techniques does not appear to detrimentally impact survival.