A subgroup of patients with normal stress myocardial perfusion imaging (MPI) have obstructive coronary artery disease (CAD) on coronary computed tomographic angiography (CCTA). A retrospective study was performed to identify factors associated with obstructive CAD in patients with normal MPI. Bivariate differences between patients with obstructive (>50% stenosis) and nonobstructive (<50% stenosis) CAD were assessed. Of the 105 patients with normal MPI, 42 (40%) had obstructive CAD on CCTA. After a multivariable logistic regression analysis increased Framingham risk scores ([FRS] ≥10%) and coronary artery calcium scores ([CACS] >100 Agatston Units [AU]) were independently associated with obstructive CAD (P = .006 and P < .0001, respectively). Patients with normal MPI had 13 times and 98 times higher odds of having obstructive CAD if they had a FRS ≥10% versus <10% and CACS >100 AU versus ≤100 AU, respectively. Increased FRS and CACS may stratify patients who may benefit from further evaluation for significant CAD despite normal MPI.