We aimed to determine the diagnostic yield and accuracy of coronary CT angiography (CCTA) in patients referred for invasive coronary angiography (ICA) based on clinical concern for coronary artery disease (CAD) and an abnormal nuclear stress myocardial perfusion imaging (MPI) study. We enrolled 100 patients (84 male, mean age 59.6 ± 8.9 years) with an abnormal MPI study and subsequent referral for ICA. Each patient underwent CCTA prior to ICA. We analyzed the prevalence of potentially obstructive CAD (≥50% stenosis) on CCTA and calculated the diagnostic accuracy of ≥50% stenosis on CCTA for the detection of clinically significant CAD on ICA (defined as any ≥70% stenosis or ≥50% left main stenosis). On CCTA, 54 patients had at least one ≥50% stenosis. With ICA, 45 patients demonstrated clinically significant CAD. A positive CCTA had 100% sensitivity and 84% specificity with a 100% negative predictive value and 83% positive predictive value for clinically significant CAD on a per patient basis in MPI positive symptomatic patients. In conclusion, almost half (48%) of patients with suspected CAD and an abnormal MPI study demonstrate no obstructive CAD on CCTA.