OBJECTIVE Automated software tools have permitted more comprehensive, robust and reproducible quantification of coronary stenosis, plaque burden and plaque location of coronary computed tomography angiography (CTA) data. The association between these quantitative CTA (QCT) parameters and the presence of myocardial ischaemia has not been explored. The aim of the present investigation was to evaluate the association between QCT parameters of coronary artery lesions and the presence of myocardial ischaemia on gated myocardial perfusion single-photon emission CT (SPECT). METHODS Included in the study were 40 patients (mean age 58.2 ± 10.9 years, 27 men) with known or suspected coronary artery disease (CAD) who had undergone multidetector row CTA and gated myocardial perfusion SPECT within 6 months. From the CTA datasets, vessel-based and lesion-based visual analyses were performed. Consecutively, lesion-based QCT was performed to assess plaque length, plaque burden, percentage lumen area stenosis and remodelling index. Subsequently, the presence of myocardial ischaemia was assessed using the summed difference score (SDS ≥2) on gated myocardial perfusion SPECT. RESULTS Myocardial ischaemia was seen in 25 patients (62.5%) in 37 vascular territories. Quantitatively assessed significant stenosis and quantitatively assessed lesion length were independently associated with myocardial ischaemia (OR 7.72, 95% CI 2.41-24.7, p < 0.001, and OR 1.07, 95% CI 1.00-1.45, p = 0.032, respectively) after correcting for clinical variables and visually assessed significant stenosis. The addition of quantitatively assessed significant stenosis (χ(2) = 20.7) and lesion length (χ(2) = 26.0) to the clinical variables and the visual assessment (χ(2) = 5.9) had incremental value in the association with myocardial ischaemia. CONCLUSIONS Coronary lesion length and quantitatively assessed significant stenosis were independently associated with myocardial ischaemia. Both quantitative parameters have incremental value over baseline variables and visually assessed significant stenosis. Potentially, QCT can refine assessment of CAD, which may be of potential use for identification of patients with myocardial ischaemia.