Abstract Aim To investigate the influence of cancer cachexia on outcomes and clinicopathological variables in pancreatico-biliary malignancies. Method Patients who underwent pancreaticoduodenectomy for malignancy from 2007-2020 at the Glasgow Royal Infirmary were included in this study. Pre-operative single-slice CT scan images were collected for cross sectional analysis of body composition using the semi-automated segmentation programme, SliceOmatic. Body composition measurements were represented as z-scores to account for age and sex. Results Subcutaneous fat radiodensity (SFD) was significantly lower in ampullary adenocarcinoma (-0.17+/-0.95), duodenal adenocarcinoma (-0.03+/-1.08), and cholangiocarcinoma (-0.18+/-1.00) groups compared to the pancreatic cancer group (0.12+/-1.00) (P=0.09). Skeletal muscle index (SMI) was significantly higher in those diagnosed with cholangiocarcinoma compared to all other indications (0.20+/-0.91 vs -0.04+/-1.02, P=0.05). Disease-specific and recurrence-free median survival was lower in those with low SMI compared to those with high SMI for all indications (35 months vs 41 months, 13 months vs 18 months).When comparing those who underwent up-front resection to those who received neoadjuvant therapy, visceral fat index (VFI) was found to be higher (0.06+/-1.00 vs -0.21+/-0.99, P=0.03) and skeletal muscle density was found to be lower (-0.05+/-1.01 vs 0.18+/-0.96, P=0.04). SFD was also found to be significantly lower in those with AJCC stage 1 compared to all other stages (-0.21+/-0.86 vs 0.07+/-1.01, P=0.03). Conclusions Adverse body composition may influence outcomes in pancreatic and biliary malignancy; however, this influence appears to be modest at best. Clinical applications of body composition analysis may be limited to serial monitoring of patients within the context of their treatment pathway.