Abstract Aims In patients with stable coronary artery disease (CAD) and high-risk plaques (HRPs) on coronary computed tomography angiography (CTA), we sought to define qualitative and quantitative CTA predictors of abnormal coronary 18F-sodium fluoride uptake (18F-NaF) by positron emission tomography (PET). Methods and results Patients undergoing coronary CTA were screened for HRP. Those who presented with ≥3 CTA adverse plaque features (APFs) including positive remodelling; low attenuation plaque (LAP, <30 HU), spotty calcification; obstructive coronary stenosis ≥50%; plaque volume >100 mm3 were recruited for 18F-NaF PET. In lesions with stenosis ≥25%, quantitative plaque analysis and maximum 18F-NaF target to background ratios (TBRs) were measured. Of 55 patients, 35 (64%) manifested coronary 18F-NaF uptake. Of 68 high-risk lesions 49 (70%) had increased PET tracer activity. Of the APFs, LAP had the highest sensitivity (39.4%) and specificity (98.3%) for predicting 18F-NaF uptake. TBR values were higher in lesions with LAP compared to those without [1.6 (1.3–1.8) vs. 1.1 (1.0–1.3), P = 0.01]. On adjusted multivariable regression analysis, LAP (both qualitative and quantitative) was independently associated with plaque TBR [LAP qualitative: β = 0.47, 95% confidence interval (CI) 0.30–0.65; P < 0.001] and (LAP volume: β = 0.20 per 10 mm3, 95% CI 0.13–0.27; P < 0.001). Conclusion In stable CAD patients with HRP, LAP is predictive of 18F-NaF coronary uptake, but 18F-NaF is often seen in the absence of LAP. If 18F-NaF uptake is shown to be associated with adverse outcomes and becomes clinically used, the presence of LAP may define patients who would not benefit from the added testing.