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Age is becoming less of a consideration to aggressive medical and surgical interventions. The aim of this study was to evaluate whether patients older than 80 years showed similar gains from total parenteral nutrition (TPN) in terms of nutritional and inflammatory markers compared to patients 35 to 50 years old. A database of patients aged ≥80 years old (group 1) and patients between 35 and 50 (group 2), on TPN for greater than 1 week, was compiled from the Nutrition Support Service (NSS) database. Patients had C-reactive protein (CRP), prealbumin, and albumin drawn twice weekly. Patients were matched 1:1 based on gender, diabetes, smoking, Subjective Global Assessment score, and diagnosis. Both groups showed comparable improvements in nutritional and inflammatory markers. There were no statistically significant differences in weekly changes to prealbumin, albumin, CRP, and CRP:prealbumin (C:P) ratio between group 1 and group 2 patients. Both groups had similar complication rates (line-related thrombosis, catheter-related bloodstream infections, intra-abdominal sepsis), days on TPN, length of hospitalization, and mortality rate. Patients older than 80 years benefit from aggressive nutritional support by administration of TPN. Age should not be used as an exclusion criterion for patients requiring TPN.