PURPOSE: To determine if a high-intensity functional exercise program improves balance, gait ability, and lower-limb strength in older people dependent in activities of daily living (ADL), if an intake of protein-enriched energy supplement immediately after the exercises increases these effects of the training, and if the exercise program reduces falls. RELEVANCE: Impairments in physical functions among older people can lead to dramatic consequences for the individual such as admission to nursing home, falls and fractures. High-intensity exercise programs are effective to improve physical functions among older people but knowledge is limited concerning the effects for older people with severe cognitive or physical impairments. PARTICIPANTS: 191 older people dependent in ADL, living in residential care facilities, and with a Mini-Mental State Examination (MMSE) score of ≥ 10 participated in this study (the FOPANU Study). METHODS: The participants were randomized to a high-intensity functional weight-bearing exercise program (the HIFE Program) or a control activity, including 29 sessions over 3 months, as well as to protein-enriched energy supplement or placebo. Berg Balance Scale, usual and maximum gait speed, and one-repetition maximum in lower-limb strength were followed-up at 3 and 6 months by assessors blinded to group allocation. Fall rate and the proportion of participants sustaining a fall during the six months following the intervention were the outcome measures of the fall preventive effect of the exercise program. ANALYSIS: The intention-to-treat principle was used. Balance, gait ability, and lower-limb strength: 2 x 2 factorial ANCOVA. Falls: Negative binominal analysis and logistic regression analysis. RESULTS: At 3 months, the exercise group had improved significantly in usual gait speed compared with the control group (mean difference 0.04 m/s, P = 0.02). At 6 months, there were significant improvements favoring the exercise group for Berg Balance Scale (1.9 points, P = 0.05), usual gait speed (0.05 m/s, P = 0.009), and lower-limb strength (10.8 kg, P = 0.03). No interaction effects were seen between the exercise and nutrition interventions. When all participants were compared, no statistically significant differences between groups were found for fall rate (exercise group 3.6 falls per person years and control group 4.6 fall per person years) or the proportion of participants sustaining a fall (exercise 53% and control 51%). A subgroup interaction analysis revealed that among participants who improved their balance during the intervention period, the exercise group had a lower fall rate than the control group (exercise 2.7 falls per person years and control 5.9 falls per person years, incidence rate ratio 0.44, P = 0.03). CONCLUSIONS: A high-intensity functional exercise program has positive long-term effects in balance, gait ability, and lower-limb strength for older people who are dependent in ADL. An intake of protein-enriched energy supplement immediately after the exercises does not appear to increase these effects of the training. In addition, the high-intensity functional exercise program may have an effect in preventing falls among those who respond to the intervention. IMPLICATIONS: High-intensity functional exercise can be offered to improve physical functions among older people who are living in residential care facilities and have severe cognitive or physical impairments.