IntroductionNutritional ultrasound (US) is an emerging technique in clinical nutrition for the morphological and structural study of muscle mass. Currently, all definitions of malnutrition include the measurement of muscle mass; however, there is no single way to assess it. It is necessary to develop new techniques to identify muscle involvement in malnutrition that are valid, standardised, reliable, accurate and profitable.ObjectiveTo value the new muscle US techniques aimed to measure muscle and functional status, to make a more accurate diagnosis and a better prediction of complications and morbidity and mortality in patients at nutritional risk. Primary outcome: to assess the feasibility of US or muscle US techniques in both nutritional diagnosis and follow-up in a nutritional intervention programme.Methods and analysisDisease-Related caloric-protein malnutrition EChOgraphy (DRECO) is a prospective, multicentre (25 Spanish hospitals), uncontrolled clinical study in standard clinical practice to value the usefulness of nutritional US (muscle US) in the nutritional diagnosis and follow-up, over 3–6 months, after standard nutritional clinical practice intervention and physical activity, to control their disease-related malnutrition. 1000 patients are expected to be included in.DiscussionThis study will standardise nutritional US measures. It will validate and define specific cut-off values for nutritional US and correlate it with already well-known nutritional tools such as Subjective Global Assessment or Global Leadership Initiative on Malnutrition criteria. Thus, muscle US will become not only a tool to diagnose malnutrition, but it will also be integrated in the daily practice to evaluate nutritional interventions.Ethics and disseminationAll DRECO study materials have been approved by each of the IRB/IEC of all the sites enrolled (either approval of the own IRB/IEC or validating the approval of the IRB/IEC of another hospital). The study has been registered with ClinicalTrials.gov, on 27 June 2022. The results from this study will be presented at scientific conferences and in peer-reviewed scientific journals.Trial registration numberNCT05433831.