Malnutrition is a costly problem for health care systems internationally. Malnourished individuals require longer hospital stays and more intensive nursing care than adequately nourished individuals and have been estimated to cost an additional £7.3 billion in health care expenditures in the United Kingdom alone. However, treatments for malnutrition have rarely been considered from an economic perspective. The aim of this systematic review was to identify the cost effectiveness of using protein and energy supplementation as a widely used intervention to treat adults with and at risk of malnutrition. Papers were identified that included economic evaluations of protein or energy supplementation for the treatment or prevention of malnutrition in adults. While the variety of outcome measures reported for cost-effectiveness studies made synthesis of results challenging, cost-benefit studies indicated that the savings for the health system could be substantial due to reduced lengths of hospital stay and less intensive use of health services after discharge. In summary, the available economic evidence indicates that protein and energy supplementation in treatment or prevention of malnutrition provides an opportunity to improve patient wellbeing and lower health system costs.