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Immunonutrition is prescribed systematically before major oncologic surgery to treat a potential malnutrition according to international guidelines. The preoperative use of immunonutrition is based on a decrease of infection and length of hospital stay after surgery. We report no association between immunonutrition and postoperative morbidity neither on infectious complications.The objective of the present study was to assess the effect of preoperative immunonutrition on a nationwide scale.According to international guidelines, immunonutrition should be prescribed before major oncologic digestive surgery to decrease postoperative morbidity. Nevertheless, this practice remains controversial.We used a prospective national health database named “Echantillon généraliste des Bénéficiaires.” Patients were selected with ICD10 codes of cancer and digestive surgery act-procedures from 2012 to 2016. Two groups were identified: with reimbursement of immunonutrition 45 days before surgery (IN-group) or not (no-IN-group). Primary outcome was 90-day severe morbidity. Secondary outcomes were postoperative length of stay (LOS) and overall survival. Logistic regression and survival analysis adjusted with IPW method were performed.One thousand seven hundred seventy-one patients were included. The proportion of different cancers was as follows: 72% patients were included in the colorectal group, 14% in the hepato-pancreato-biliary group, and 12% in the upper gastrointestinal group. Patients from the IN-group (n = 606, 34%) were younger (67.1 ± 11.8 vs 69.2 ± 12.2 years, P < 0.001), with increased use of other oral nutritional supplements (49.5% vs 31.8%, P < 0.001) and had more digestive anastomoses (89.4% vs 83.0%, P < 0.001). There was no significant difference between the 2 groups for 90-day severe morbidity [odds ratio (OR): 0.91, 95% confidence interval (95% CI): 0.73–1.14] or in survival (hazard ratio: 0.89, 95% CI: 0.73–1.08). LOS were shorter in the IN-group [−1.26 days, 95% CI: −2.4 to −0.1)].The preoperative use of immunonutrition before major oncologic digestive surgery was not associated with any significant difference in morbidity or mortality. However, the LOS was significantly shorter in the IN-group.