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Physical inactivity is an established independent risk factor for cardiovascular disease (CVD), the leading cause of death and disability among U.S. adults. Information on the economic impact of CVD associated with inactivity is lacking, however, although it is needed to attract more resources for preventing CVD and promoting physical activity.The objective of this study was to estimate the direct medical expenditures of CVD associated with inactivity.A population-based analysis of direct medical expenditures was performed by linking the 1996 Medical Expenditure Panel Survey to the 1995 National Health Interview Survey. The study participants were adults (N = 2,472; ages ≥ 19 years; not pregnant) in the noninstitutionalized, civilian population in 1996. Medical expenditures associated with inactivity were derived by comparing the medical expenditures between population groups stratified by physical activity and CVD status.In 1996, the prevalence of physical inactivity was 47.5%. The overall prevalence of CVD was 21.5% (16.7% in active persons, 23.6% in inactive persons, and 49.5% in persons with physical limitations). In this population, there were 7.3 million CVD cases; 1.1 million of them (15.3%) were associated with inactivity. The total medical expenditure of persons with CVD was $41.3 billion, of which $5.4 billion (13.1%) was associated with inactivity. Applying these percentages to the total health and economic burdens of CVD in the United States, there were 9.2 million CVD cases ($23.7 billion direct medical expenditure) associated with inactivity in 2001.The high economic burden of inactivity-associated CVD demonstrates the need to promote physical activity among U.S. adults.