Abstract Introduction: Obesity, defined as a body mass index (BMI) > 30 kg/m2, increases the risk of benign and malignant pancreatic diseases. One mainstay of treatment for certain pancreatic conditions involves surgical resection with pancreaticoduodenectomy, a technically complex operation with high complication risk. In this analysis, we hypothesized that obesity and morbid obesity would adversely impact perioperative outcomes for the pancreaticoduodenectomy procedure. Methods: Retrospective study design using a large, single institution surgical database (2004-2024; n = 948) that was queried for non-underweight, non-metastatic pancreatic diseases treated with pancreaticoduodenectomy. Patients were categorized as non- obese (BMI < 30), obese (BMI >/= 30), or morbid obesity (BMI >/= 40) based on pre-operative BMI. Odds Ratio (OR) of having a post-operative complication was the primary outcome. Results: In this study, 948 patients were included for analysis. Compared to non- obese (n=675) patients, obesity (n=273) was associated with increased frequency of biliary fistula (2.6% vs. 0.9%, p = 0.036), urinary retention (9.9% and 5.8%, p = 0.013), longer mean operating time (451.5 vs. 425.9 minutes, p = 0.0009), higher intraoperative blood loss (150 mL vs 100 mL, p = 0.007), and smaller pancreatic duct diameter (3.4 vs 4.9 mm, p = 0.0008). On sub-analysis, compared to non-obese patients, morbid obesity (n=75) was associated with increased frequency of wound seroma (5.3% vs.1.6%, p=0.018), higher 90-day mortality (5.3% vs. 1.6%, p=0.016), longer mean operating time (482.6 vs. 429.0 minutes, p<0.0001), higher intraoperative blood loss (150 vs. 120 mL, p=0.032), smaller pancreatic duct diameter (3.3 vs. 3.8 mm, p=0.041), greater intraoperative fluids administration (4306. vs. 3673.9 mL, p = 0.009), and longer hospital length of stay (9.1 vs. 7.1 days, p = 0.014). Although obese and morbidly obese patients experienced longer and more challenging operations, the overall risk of experiencing any postoperative complication was not significantly different compared to non- obese patients on adjusted analysis. Conclusions: Obesity and morbid obesity are associated with longer and more technically challenging pancreatic operations. However, contrary to our hypothesis, this increase in surgical complexity was not associated with a significantly increased risk of postoperative complicationson adjusted analysis. Citation Format: Hannah M Engebretson, Kyle W Blackburn, Centura R Anbarasu, Cary M Hsu, Eric J Silberfein, Samir S Awad, Eugene A Choi, Christy Y Chai, Ramsey E Camp, George M Van Buren, William E Fisher, Derek J Erstad. Impact of obesity on Pancreaticoduodenectomy procedure perioperative outcomes [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr B003.