We sought to clarify the significance of cardiac dysfunction and to assess its relationship with elevated biomarkers by using cardiovascular magnetic resonance imaging in healthy, middle-aged subjects immediately after they ran 26.2 miles. Cardiac dysfunction and elevated blood markers of myocardial injury have been reported after prolonged strenuous exercise. From 425 volunteers, 13 women and 12 men were randomly selected, provided medical and training history, and underwent baseline cardiopulmonary exercise testing to exhaustion. Blood biomarkers, cardiovascular magnetic resonance imaging, and 24-h ambulatory electrocardiography were performed 4 wk before and immediately after the race. Participants were 38.7+/-9.0 yr old, had baseline peak oxygen consumption of 52.9+/-5.6 ml.kg(-1).min(-1), and completed the marathon in 256.2+/-43.5 min. Cardiac troponin I and B-type natriuretic peptide increased following the race (P=0.001 and P<0.0001, respectively). Cardiovascular magnetic resonance-determined pre- and postmarathon left ventricular ejection fractions were comparable, 57.7+/-4.1% and 58.7+/-4.3%, respectively (P=0.32). Right atrial volume index increased from 46.7+/-14.4 to 57.0+/-14.5 ml/m2 (P<0.0001). Similarly, right ventricular end-systolic volume index increased from 47.4+/-11.2 to 57.0+/-14.6 ml/m2 (P<0.0001) whereas the right ventricular ejection fraction dropped from 53.6+/-7.1 to 45.5+/-8.5% (P<0.0001). There were no morphological changes observed in the left atrium or ventricle or evidence of ischemic injury to any chamber by late gadolinium enhancement. There were no significant arrhythmias. Marathon running causes dilation of the right atrium and right ventricle, reduction of right ventricular ejection fraction, and release of cardiac troponin I and B-type natriuretic peptide but does not appear to result in ischemic injury to any chamber.