Detection of subclinical coronary atherosclerosis is possible using exercise myocardial perfusion imaging for inducible ischemia or multidetector computed tomography for coronary artery calcium (CAC), which is used to detect subclinical coronary atherosclerosis. The extent to which these screening tests converge in an asymptomatic population that is at increased risk for coronary artery disease remains unknown. We compared the concordance of findings in 260 asymptomatic middle-age siblings of hospitalized index patients <60 years of age with documented coronary artery disease. All subjects underwent maximal exercise testing with postexercise and delayed attenuation-corrected thallium single-photon emission computed tomography and multidetector computed tomography for CAC. An abnormal exercise single-photon emission computed tomographic (SPECT) result occurred in >50% of subjects with a CAC score >100, but also in 12% with no CAC, 9% with CAC scores of 1 to 10, and 20% with CAC scores of 11 to 100. In subjects with an abnormal exercise SPECT result, 59% had CAC scores < or =100. Overall, there was only a modest agreement between an abnormal exercise SPECT result and high CAC scores. In conclusion, although moderate or severe CAC is often associated with inducible ischemia, the absence of CAC or the presence of only mild CAC by no means precludes inducible myocardial ischemia. These screening tests may reflect different aspects or stages of coronary disease in an asymptomatic middle-age population.