BACKGROUND & AIMS: Previous studies reported a severely impaired energy balance in COPD patients during the first days of an acute exacerbation, mainly due to a decreased energy and protein intake. The aim of the study was to investigate the feasibility and effectiveness of energy- and protein-rich nutritional supplements during hospitalization for an acute exacerbation in nutritionally depleted COPD patients. METHODS: In a randomized double-blind, placebo-controlled two-center trial, 56 COPD patients were randomized and 47 patients completed the study. Nutritional intervention consisted of 3 x 125 ml (2.38 MJ/day) and the placebo group received similar amounts of a non-caloric fluid. Medical therapy and dietetic consultation were standardized and dietary intake was measured daily. Body composition, respiratory and skeletal muscle strength, lung function and symptoms were measured on admission and on days 4 and 8 of hospitalization. RESULTS: Forty-seven percent of the patients had experienced recent involuntary weight loss prior to admission. The degree of weight loss was inversely related to resting arterial oxygen tension (r = 0.31; P < 0.05). Nutritional intervention resulted in a significant increase in energy (16% vs. placebo) and protein intake (38% vs. placebo). Mean duration of hospitalization was 9 +/- 2 days. Relative to usual care, no additional improvements in lung function or muscle strength were seen after nutritional intervention. CONCLUSIONS: Oral nutritional supplementation during hospitalization for an acute exacerbation is feasible in nutritionally depleted COPD patients and does not interfere with normal dietary intake.