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Objective: The aim of this study was to evaluate whether patients with nonalcoholic fatty liver disease (NAFLD) have more myocardial malperfusion on CT myocardial perfusion imaging (CT-MPI), as well as to further assess if NAFLD is a predictor of myocardial ischemia independently., Methods: A total of 310 consecutive patients were included for analysis. All patients were divided into two groups according to the presence or absence of NAFLD, which was diagnosed by noncontrast cardiac CT partially covered liver and spleen. Clinical characteristics as well as imaging features including coronary artery calcium score, CCTA, and CT-MPI findings were analyzed. Univariable and multivariable logistic regression analyses were used to find out the relationship between NAFLD and myocardial ischemia., Results: NAFLD (unadjusted hazard ratio [HR]: 2.4, 95% confidence interval [CI]: 1.2 to 4.4, p = 0.008), male (HR: 2.6, 95% CI: 1.5 to 4.5, p = 0.001), obstructive CAD (HR: 2.3, 95% CI: 1.3 to 4.2, p = 0.004), and FAI ≥ -70.1 HU (HR: 3.1, 95% CI: 1.8 to 5.5, p < 0.001) were associated with myocardial ischemia in univariable analysis. After adjusting for traditional CAD risk factors and CT characteristics in the multivariable regression analysis, NAFLD (HR: 2.3, 95% CI: 1.2 to 4.4, p = 0.016) was an independent predictor of myocardial ischemia., Conclusion: Our data suggest that myocardial ischemia was more prevalent in patients with NAFLD, and NAFLD is a predictor of myocardial ischemia independent of traditional cardiovascular risk factors and CCTA characteristics., Key Points: • NAFLD patients had higher calcium score, incidence of obstructive coronary artery disease, grade of CAD-RADS, quantitative plaque characteristics, and incidence of fat attenuation index ≥ -70.1 HU. • NAFLD patients had a higher incidence of myocardial ischemia, myocardial hypoperfusion, and hypoperfusion myocardial segments ratio. • NAFLD was a predictor of myocardial ischemia, independent of traditional cardiovascular risk factors, and CCTA characteristics., (© 2022. The Author(s), under exclusive licence to European Society of Radiology.)