The measurement of the amount of energy utilized during physical activity has generated considerable interests from various groups ranging from exercise physiologists to nutritionists and fitness center workers. To date, however, the existing energy expenditure estimation methods are not so reliable and compact. In this paper, we propose a new method for accurately and easily estimating energy expenditure during physical activity with a novel algorithm. This method involves acquiring acceleration signals through a 15-channel whole-body segment acceleration measurement system and then estimating the calories expended using a newly developed algorithm. The results of 3 subjects' experiments were compared with a commercially available mask type indirect calorimeter and a 9-axis accelerometry-based calorimeter. The results demonstrate that the proposed method provides a new and reliable way to estimate human energy expenditure during physical activity.