CT angiography (CTA) and SPECT myocardial perfusion imaging (MPI) are complementary imaging techniques to assess coronary artery disease (CAD). Spatial integration and combined visualization of SPECT MPI and CTA data may facilitate correlation of myocardial perfusion defects and subtending coronary arteries and thus offer additional diagnostic value over either stand-alone or side-by-side interpretation of the respective datasets from the 2 modalities. In this study, we investigated the additional diagnostic value of a software-based CTA/SPECT MPI image fusion system over conventional side-by-side analysis in patients with suspected CAD. Methods: Seventeen symptomatic patients who underwent both CTA and SPECT MPI within a 90-d period were included in our study; 7 of them also underwent invasive coronary angiography (ICA). The potential benefits of the synchronized multimodal heart visualization (SMARTVis) system in assessing CAD were investigated through a case study involving 4 experts from 2 medical centers, in which we performed, first, a side-by-side analysis using structured CTA and SPECT reports and, second, an integrated analysis using the SMARTVis system in addition to the reports. Results: The fused interpretation led to a more accurate diagnosis, reflected in an increase in the individual observers' sensitivity and specificity to correctly refer for invasive angiography eventually followed by revascularization. For the first, second, third, and fourth observers, the respective sensitivities improved from 50%, 60%, 80%, and 80% to 70%, 80%, 100%, and 90% and the respective specificities from 100%, 94%, 83%, and 83% to 100%, 100%, 94%, and 83%. Additionally, the interobserver diagnosis agreement increased from 74% to 84%. The improvement was primarily found in patients presenting with CAD in more vessels than the number of reported perfusion defects. Conclusion: Integrated analysis of cardiac CTA and SPECT MPI using the SMARTVis system results in an improved diagnostic performance.