e16270 Background: Blood transfusion is associated with a negative impact on cancer survival. This study aims to evaluate intra-operative time (OR time) and estimated blood loss (EBL) and their impact on survival. Methods: A retrospective review was undertaken to identify patients who had pancreaticoduodenectomy, treated at one of our 4 HPB centers of excellence for Northern California Kaiser Permanente members. All patients received their treatments between January 2015 and July 2022. The two parameters of OR time and EBL were assigned into a 2x2 grid with the creation of four separate groups. The 4 combination groups identified patients with an OR time of more than 400 minutes as time being compared and EBL of more than 600 ml as the absolute volume compared. Results: We identified 999 patients who underwent a pancreaticoduodenectomy. The mean OR time was 377 minutes, and the mean EBL was 349 ml. Portal vein resection was performed on 10.8% of patients. Neoadjuvant chemotherapy (NAT) was used in 27.8% of patients and associated with longer OR time, EBL, and portal vein resection (p<.001). Patients with OR time >400 minutes and EBL >600 ml was associated with male, higher percentage of pancreatic/bile duct cancer, portal vein resection, a longer length of stay, re-admission at 7- and 30-days post-op, neoadjuvant chemotherapy, and adjuvant chemotherapy (Table 1). Mean overall survival for the patients with an OR time >400 minutes and EBL >600 ml was 37 months, while for those with an OR time <400 minutes and EBL <600 ml was 59 months (p<.001). Conclusions: The combination of prolonged intra-operative time and blood loss is associated with decreased overall survival. The two parameters of EBL and OR time are a proxy for advanced tumors and vascular involvement gave the need for portal vein resection and higher utilization of adjuvant and neoadjuvant chemotherapy.