Abstract Aims Preoperative nutritional status of patients who undergo surgery due to hepato-pancreato-biliary (HPB) cancer has been considered as a prognostic factor of their postoperative course. The aim of the present study was to investigate the association of preoperative nutritional assessment with the postoperative morbidity and mortality in such patients. Methods Patients undergoing surgery due to HPB cancer from March 2022 until March 2023 at two university surgical departments were included in the present study. Patients’ demographics and postoperative parameters, such as complications’ severity according to Clavien-Dindo classification and mortality, along with malignancy stage were reported. Preoperative nutritional assessment was conducted according to the Global Leadership Initiative on Malnutrition (GLIM) criteria and the Controlling Nutritional Status (CONUT) score. The present study was registered in ClinicalTrials.gov (NCT05795374). Results The present study included 66 patients with a mean age of 63 ± 12 years old. The high risk of malnutrition according to the GLIM criteria was associated with major (Clavien-Dindo≥3) postoperative complications (74% vs 32%, p=0.026) and increased 30-day mortality (80% vs 23%, p=0.021). Moreover, malnutrition according to the CONUT tool was correlated to increased 30-day mortality (66% vs 45%, p=0.016). Conclusions Preoperative malnutrition seems to be associated with higher rates of postoperative mortality and major morbidity in patients undergoing surgery due to HPB cancer.