Background Impaired global coronary flow reserve (g-CFR) is related to worse outcomes. Inflammation has been postulated to play a role in atherosclerosis. This study aimed to evaluate the relationship between pre-procedural pericoronary adipose tissue inflammation and g-CFR after the urgent percutaneous coronary intervention in patients with first non-ST-segment-elevation acute coronary syndrome. Methods and Results Phase-contrast cine-magnetic resonance imaging was performed to obtain g-CFR by quantifying coronary sinus flow at 1 month after percutaneous coronary intervention in a total of 116 first non-ST-segment-elevation acute coronary syndrome patients who underwent pre-percutaneous coronary intervention computed tomography angiography. On proximal 40-mm segments of 3 major coronary vessels on computed tomography angiography, pericoronary adipose tissue attenuation was assessed by the crude analysis of mean computed tomography attenuation value. The patients were divided into 2 groups with and without impaired g-CFR divided by the g-CFR value of 1.8. There were significant differences in age, culprit lesion location, N-terminal pro-B-type natriuretic peptide levels, high-sensitivity C-reactive protein (hs-CRP) levels, mean pericoronary adipose tissue attenuation between patients with impaired g-CFR and those without (g-CFR, 1.47 1.16, 1.68 versus 2.66 2.22, 3.28; <0.001). Multivariable logistic regression analysis revealed that age (odds ratio OR, 1.060; 95% CI, 1.012-1.111, =0.015) and mean pericoronary adipose tissue attenuation (OR, 1.108; 95% CI, 1.026-1.197, =0.009) were independent predictors of impaired g-CFR (g-CFR <1.8). Conclusions Mean pericoronary adipose tissue attenuation, a marker of perivascular inflammation, obtained by computed tomography angiography performed before urgent percutaneous coronary intervention, but not hs-CRP, a marker of systemic inflammation was significantly associated with g-CFR at 1-month after revascularization. Our results may suggest the pathophysiological mechanisms linking perivascular inflammation and g-CFR in patients with non-ST-segment-elevation acute coronary syndrome.