Aim The use of concentrated oral nutrition supplements dispensed in small volumes throughout the day at medication rounds is a common nutrition support strategy. Often termed 'Nutrition as Medication' or NAM, it is associated with excellent rates of patient consumption. However, administration of NAM has been described as suboptimal. The aim of the present study was to identify and explore factors influencing the efficacy of the NAM program from a qualitative perspective. This included exploring issues relating to knowledge, administration and patient consumption from a patient and health professional perspective. Methods Semistructured interviews with patients (n = 7) and eight focus groups with nursing, medical, pharmacy and dietetic staff (n = 63) were conducted. Interviews were conducted in the workplace and were recorded and transcribed verbatim. Data were analysed from a realist theoretical position using the thematic framework approach. Results Five themes were identified that impact on the efficacy of the NAM program. These include the need for clear role delineation among health professionals regarding responsibility for each aspect of NAM. Other themes that emerged included misconceptions about the importance and relevance of the treatment; perceptions of poor palatability and issues associated with the logistics of providing the supplements within the hospital setting. Conclusions Dietitians should be aware that there are a range of factors that influence the efficacy of the NAM strategy, including the knowledge and values of individual health professional staff. In addition, increased awareness is required by dietitians regarding the structural barriers to administration and receiving of NAM at the ward level.