Clinical care and enteral feeding of long-term ventilator-dependent overweight patients are difficult. The caloric recommendation for non-critically ill patients is 20～25 kcal/kg actual weight（wt.）/day as suggested by the European Society for Parenteral and Enteral Nutrition. The Society of Critical Care Medicine/American Society for Parenteral and Enteral Nutrition suggests a caloric intake of 11～14 kcal/kg actual wt. /day. This study evaluated whether a hypocaloric, nutrient-complete, highprotein formula can induce weight loss but maintain the nutritional status in long-term ventilator-dependent overweight patients. Patients who had stayed in a respiratory care unit for over a year and had a body mass index（BMI）of 24 kg/m2 were enrolled. Exclusion criteria included patients with poor kidney function and edema. Patients in the cohort were given a modulated, nutrient-complete, high-protein formula with 16.2 ± 2.6 kcal/kg actual wt.（protein: fat: carbohydrate of 24%: 23%: 53%）for 4 months. They were checked monthly for weight and nutrition-related biochemical data. In a comparison of 4-months pre- and post-intervention results, patients' BMI values significantly dropped from 26.4 ±3.4 to 25.2 ± 2.7 kg/m2. Albumin significantly increased from 3.39 ± 0.46 to 3.59 ± 0.45 g/dl in 4 months. Total protein also significantly increased after the intervention. Other biochemical data such as white blood cells, hemoglobin, blood urea nitrogen, creatinine, sodium, and potassium were all maintained within a normal range. In conclusion, a hypocaloric, nutrient-complete, high-protein formula selected by dietitians can induce weight loss while maintaining the nutritional status in long-term ventilator-dependent overweight patients.