Lack of physical activity (PA) increases risk of coronary heart disease. Metabolic risk factors increase the risk of coronary heart disease and development of advanced coronary artery calcium (CAC). We hypothesized that, in a population with multiple metabolic risk factors (> or =2), the degree of PA would be inversely associated with the degree and prevalence of CAC. After excluding subjects who had known diabetes and coronary heart disease, we studied 779 asymptomatic patients referred for electron beam tomography. All patients had > or =2 of the following metabolic risk factors: blood pressure > 130/85 mm Hg, serum triglycerides >150 mg/dl, serum high-density lipoprotein < 40 and < 50 mg/dl in men and women, respectively, and body mass index >30 kg/m(2). Advanced CAC was defined as a calcium score >75th percentile based on gender and age. In the study, 37% patients were sedentary, 26% engaged in moderate-duration (< 30 minutes 1 to 2 times/week) PA, and 37% engaged in long-duration (> or =30 minutes > or =3 times/week) PA. The median CAC scores were 24 (sedentary), 18 (moderate PA), and 11 (long-duration PA; p <0.002). Advanced CAC was prevalent in 26% of sedentary patients, 24% of patients who performed moderate PA, and 16% of patients who engaged in long-duration PA (p <0.05). On logistic regression analysis, long-duration PA had an independent inverse association with advanced CAC. Thus, asymptomatic patients who have > or =2 metabolic risk factors and who regularly engage in long-duration PA have a lower prevalence of CAC than do those who are sedentary or participate in moderate-duration PA.