PurposeThe purpose of this study was to evaluate the diagnostic performance of automated deep learning in the detection of coronary artery disease (CAD) on photon-counting coronary CT angiography (PC-CCTA). Materials and methodsConsecutive patients with suspected CAD who underwent PC-CCTA between January 2022 and December 2023 were included in this retrospective, single-center study. Non-ultra-high resolution (UHR) PC-CCTA images were analyzed by artificial intelligence using two deep learning models (CorEx, Spimed-AI), and compared to human expert reader assessment using UHR PC-CCTA images. Diagnostic performance for global CAD assessment (at least one significant stenosis ≥ 50 %) was estimated at patient and vessel levels. ResultsA total of 140 patients (96 men, 44 women) with a median age of 60 years (first quartile, 51; third quartile, 68) were evaluated. Significant CAD on UHR PC-CCTA was present in 36/140 patients (25.7 %). The sensitivity, specificity, accuracy, positive predictive value), and negative predictive value of deep learning-based CAD were 97.2 %, 81.7 %, 85.7 %, 64.8 %, and 98.9 %, respectively, at the patient level and 96.6 %, 86.7 %, 88.1 %, 53.8 %, and 99.4 %, respectively, at the vessel level. The area under the receiver operating characteristic curve was 0.90 (95 % CI: 0.83–0.94) at the patient level and 0.92 (95 % CI: 0.89–0.94) at the vessel level. ConclusionAutomated deep learning shows remarkable performance for the diagnosis of significant CAD on non-UHR PC-CCTA images. AI pre-reading may be of supportive value to the human reader in daily clinical practice to target and validate coronary artery stenosis using UHR PC-CCTA.