Many male marathon runners have elevated coronary artery calcium (CAC) scores despite high physical activity. We examined the association between CAC scores, cardiovascular risk factors, and lifestyle habits in long-term marathoners. We recruited men who had run one or more marathons annually for 25 consecutive years. CAC was assessed using coronary computed tomography angiography. Atherosclerotic cardiovascular disease risk factors were measured with a 12-lead ECG, serum lipid panel, height, weight, resting blood pressure and heart rate, and a risk factor questionnaire. Fifty males, mean age 59 ± 0.9 yr with a combined total of 3510 marathons (median = 58.5, range = 27-171), had a mean BMI of 22.44 ± 0.4 kg·m, HDL and LDL cholesterols of 58 ± 1.6 and 112 ± 3.7 mg·dL, and CAC scores from 0 to 3153. CAC scores varied from 0 in 16 runners to 1-100 in 12, 101-400 in 12, and >400 in 10. There was no statistical difference in the number of marathons run between the four groups. Compared with marathoners with no CAC, marathoners with moderate and extensive CAC were older (P = 0.002), started running at an older age (P = 0.003), were older when they ran their first marathon (P = 0.006), and had more CAD risk factors (P = 0.005), and marathoners with more CAC had higher rates of previous tobacco use (P = 0.002) and prevalence of hyperlipidemia (P = 0.01). Among experienced males who have run marathons for 26-34 yr and completed between 27 and 171 marathons, CAC score is related to CAD risk factors and not the number of marathons run or years of running. This suggests that among long-term marathoners, more endurance exercise is not associated with an increased risk of CAC.