We evaluated a prototype SPECT system integrated with multidetector row CT (MDCT) for obtaining complementary information on coronary anatomy and hemodynamic lesion significance. Twenty-five consecutive patients with known or suspected coronary artery disease (CAD) underwent routine SPECT myocardial perfusion imaging (MPI). All patients also underwent repeat MPI with a mobile SPECT unit which could be attached to a 64-slice MDCT system. Coronary CT angiography (cCTA) was performed without repositioning the patient. Investigational MPI was compared with routine MPI for detection of myocardial perfusion defects (PD). Two observers diagnosed presence or absence of CAD based on MPI alone, cCTA alone, and based on combined MPI and cCTA with fused image display. In 22/24 patients investigative MPI corresponded with routine MPI (r = 0.80). Stenosis >or= 50% at cCTA was detected in 6/24 patients. Six out of 24 patients had PD at regular MPI. Three of these six patients had no significant stenosis at cCTA. Three out of 19 patients with normal MPI studies had significant stenosis at cCTA. Our initial experience indicates that the integration of SPECT MPI with cCTA is technically feasible and enables the comprehensive evaluation of coronary artery anatomy and myocardial perfusion with a single instrumental setup.