BACKGROUND: Supplementation with medium-chain triglycerides (MCTs) was previously shown to increase muscle function in frail elderly individuals. OBJECTIVE: We aimed to assess effects of MCTs on cognition in such individuals. METHODS: We enrolled 64 elderly nursing home residents (85.5 ± 6.8 y; 13 men, 51 women; BMI 18.6 ± 2.5 kg/m2) in a 3-mo randomized, controlled, single-blinded, intervention trial. Participants were randomly allocated to 3 groups: the first group received supplemental L-leucine (1.2 g) and cholecalciferol (20 μg) enriched with 6 g/d of MCTs (LD + MCT group) as a positive control, the second group received 6 g/d of MCTs (MCT group) as the test nutrient, and the third group received 6 g/d of long-chain triglycerides (LCT group) as a negative control. Cognition (secondary outcome) was monitored 4 times: baseline, 1.5 and 3 mo after initiation of the intervention (intervention), and 1.5 mo after termination of the intervention (postintervention follow-up). Cognition scores were assessed by a linear mixed model (intention-to-treat analysis). RESULTS: MCT supplementation increased the Mini-Mental State Examination (MMSE) score by 3.5 points at the 3-mo intervention from baseline (P < 0.001) [intention-to-treat adjusted means: baseline 17.5 points (95% CI: 14.9, 20.2), 3-mo intervention 21.0 points (18.3, 23.7)], whereas LCT supplementation decreased the MMSE score by -0.7 points [baseline 17.0 points (95% CI: 14.4, 19.6), 3-mo intervention 16.3 points (13.6, 18.9)]. At the 3-mo intervention, the difference in MMSE score between the MCT (21.0 points) and LCT (16.3 points) groups became significant (P < 0.05). The increase in MMSE score in response to MCTs was 2.1-fold greater at 3 mo than at 1.5 mo and had returned to baseline value at the 4.5-mo postintervention follow-up visit. CONCLUSION: Supplementation with 6 g MCTs/d may improve the cognition of frail elderly individuals. This trial was registered at umin.ac.jp as UMIN000023302.