Purpose: The purpose of this study was to evaluate whether adenosine-stress myocardial CT perfusion (CTP) in addition to CT angiography (CTA) improves the positive predictive value (PPV) of CT for diagnosing significant coronary artery stenoses in patients with recent acute-onset chest pain. Methods: Consecutive patients hospitalised with acute chest pain, but normal electrocardiogram and cardiac biomarkers were scheduled for CTP on top of CTA. Among patients referred for invasive coronary angiography (ICA), a per patient and per vessel analysis for the detection of coronary stenoses by CTA and reversible perfusion defects by CTP was performed. ICA including fractional flow reserve (FFR) for intermediate stenosis was used as a reference method. For the per vessel analysis, PPV was evaluated for intermediate (50-70%) and severe (>70%) coronary lesions as defined by CTA, and negative predictive value (NPV) for mild (0-49%) coronary lesions. Results: Both CTA and CTP were performed in 34 patients scheduled for ICA. ICA found significant coronary stenoses in 21 patients (62%) and per patient PPV was 76% for CTA increasing to 90% for combined CTA+CTP. Area under the curve (AUC) was 0.72 for CTA and 0.88 for CTA+CTP (p=0.02). In the per vessel analysis significant coronary stenoses were found on ICA in 32 vessels (31%), and PPV for CTA was 69% increasing to 97% for CTA+CTP. AUC was 0.88 for CTA and 0.96 for CTA+CTP (p=0.006). Of 102 vessels, CTA found mild coronary lesions in 56 vessels (55%), intermediate lesions in 15 vessels (15%) and severe lesions in 31 vessels (30%). In intermediate lesions by CTA, ICA/FFR confirmed a significant stenosis in 2/15 vessels (PPV= 13%), and for CTA+CTP PPV increased to 75%. In severe lesions by CTA, ICA confirmed a significant stenosis in 30/31 vessels (PPV=97%) and for CTA+CTP PPV was 100%. NPV was 98% for mild CTA lesions, without any additional contribution of CTP. Conclusion: In patients with recent acute-onset chest pain myocardial CT perfusion has incremental diagnostic value in addition to CT-angiography for diagnosing significant coronary stenoses. CT perfusion appears to be most beneficial in the assessment of intermediate coronary stenoses.