BACKGROUND & AIMS: The effect of nutritional supplements on mental health in older patients has received little attention so far. The aims of this trial were therefore to test the effect of nutritional support on older patient's depressive symptoms and cognitive function. METHODS: In this prospective, double-blind, placebo-controlled study, we randomly assigned 225 hospitalised acutely ill older patients to receive either normal hospital diet plus 400 mL oral nutritional supplements (106 subjects) or normal hospital diet plus a placebo (119 subjects) daily for 6 weeks. The composition of the supplement was such as to provide 995 kcal for energy and 100% of the Reference Nutrient Intakes for a healthy old person for vitamins and minerals. Outcome measures were 6 weeks and 6 months changes in nutritional status, depressive symptoms and cognitive state. RESULTS: Randomisation to the supplement group led to a significant increase in red-cell folate and plasma vitamin B12 concentrations, in contrast to a decrease seen in the placebo group. There were significant differences in symptoms of depression scores in the supplement group compared with the placebo group at 6 months (p = 0.021 for between groups difference). The effect of supplement was seen in all patient groups including those with no symptoms of depression, mild depression and those with severe depression (p = 0.007). There was no evidence of a difference in cognitive function scores at 6 months. CONCLUSION: Oral nutritional supplementation of hospitalised acutely ill older patients led to a statistically significant benefit on depressive symptoms.