Background: Malnutrition is very common among chronically hospitalized patients, especially those in the intensive care unit (ICU). Identifying the patients at risk and providing suitable nutritional support can prevent and/or overcome malnutrition in them. Total parenteral nutrition (TPN) and partial parenteral nutrition (PPN) are two common routes to deliver nutrition to hospitalized patients. We conducted a multicenter, prospective double blind randomized controlled trial to evaluate the benefits and compare their adverse effects of each method. Materials and Methods: 97 patients were enrolled and divided into two groups based on the inclusion criteria. Serum protein, serum albumin, serum transferrin, and total lymphocyte count were measured on days 7 and 14. Results: We did not find any statistically significant differences in clinical status or laboratory values between the two groups but there were significant improvements in measured lab values between days 7 and 14 (p <0.005) indicating improved nutritional status in each groups. Conclusion: This study shows that both TPN and PPN can be used safely in chronic ICU patients to provide nutritional support and prevent catabolic state among chronic critically ill patients. We need to develop precise selection criteria in order to choose the patients who would benefit the most from TPN and PPN. In addition, appropriate laboratory markers are needed to monitor the metabolic requirements of the patients and assess their progress.