OBJECTIVES: Disease-related malnutrition remains a major burden for patients and health care systems. The Medication Pass Nutritional Supplement Program (MEDPass) involves providing patients with oral nutritional supplements (ONS) in unusually small amounts three to four times per day during medication rounds. This systematic review aims to evaluate the impact of MEDPass ONS administration on compliance, total energy and protein intake, food intake, body weight and handgrip strength in hospitalized adults and nursing-home residents. METHODS: We conducted a systematic literature search in the databases MEDLINE, Embase, ScienceDirect, and the Cochrane Library and included randomized controlled trials (RCTs), non-RCTs, and before-after studies. Validated tools specific to the study design were used to assess the included studies. RESULTS: Ten studies were identified, including two RCTs, three non-RCTs, and five before-after trials. Compliance increased by 23.4% to 66% with MEDPass administration, resulting in compliance rates of 72.7% to 96%. With MEDPass administration, body weight increased by 1% to 6.8% or remained stable. The assessed evidence on total energy intake is ambiguous for protein, with a trend toward an increased intake. Trials on energy intake from food show mixed results as well. One study suggested a slight increase in handgrip strength. The included studies predominantly raise concerns for bias. CONCLUSIONS: We conclude that MEDPass ONS administration increases compliance in hospitalized adults and nursing-home residents. For all other outcomes, robust and well-powered trials are necessary.