Abstract Aims To investigate the association between pericoronary adipose tissue (PCAT) computed tomography (CT) attenuation derived from coronary computed tomography angiography (CTA) and coronary flow reserve (CFR) by positron emission tomography (PET) in patients with suspected coronary artery disease (CAD). Methods and results PCAT CT attenuation was measured in proximal segments of all major epicardial coronary vessels of 105 patients with suspected CAD. We evaluated the relationship between PCAT CT attenuation and other quantitative/qualitative CT-derived anatomic parameters with CFR by PET. Overall, the mean age was 60 ± 12 years and 93% had intermediate pre-test probability of obstructive CAD. Obstructive CAD (≥50% stenosis) was detected in 37 (35.2%) patients and impaired CFR (<2.0) in 32 (30.5%) patients. On a per-vessel analysis (315 vessels), obstructive CAD, non-calcified plaque volume, and PCAT CT attenuation were independently associated with CFR. In patients with coronary calcium score (CCS) <100, those with high-PCAT CT attenuation presented significantly lower CFR values than those with low-PCAT CT attenuation (2.47 ± 0.95 vs. 3.13 ± 0.89, P = 0.003). Among those without obstructive CAD, CFR was significantly lower in patients with high-PCAT CT attenuation (2.51 ± 0.95 vs. 3.02 ± 0.84, P = 0.021). Conclusion Coronary perivascular inflammation by CTA was independently associated with downstream myocardial perfusion by PET. In patients with low CCS or without obstructive CAD, CFR was lower in the presence of higher perivascular inflammation. PCAT CT attenuation might help identifying myocardial ischaemia particularly among patients who are traditionally considered non-high risk for future cardiovascular events.