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Background The decision-making process of patients with angiographically-intermediate coronary lesions (ICL) is clinically challenging and may benefit from adjunctive invasive techniques. Fractional-flow-reserve (FFR) represents the gold standard to evaluate ICL but frequency-domain optical-coherence-tomography (OCT) is a novel, promising, high resolution coronary imaging technique, which allows physiopathologic assessment of coronary plaque. We investigated the possible relation between OCT and FFR in selected ICL patients. Methods Stable or unstable patients with ICL who underwent both FFR and OCT assessment at two large tertiary centers were retrospectively enrolled. FFR was performed according to standard methodology. OCT images were (on blind to clinical and FFR results) analyzed to assess minimal lumen area (MLA), percentage area stenosis (AS), thrombus and plaque ulceration. Results Forty patients were identified (62 ± 10 years, 93% symptomatic, 35% acute presentation, 93% left-anterior-descending artery ICL). Percentage diameter stenosis at quantitative coronary angiography was 40 ± 12% and FFR was 0.85 ± 0.07. MLA ( p = 0.009), AS ( p < 0.001) and plaque ulceration ( p = 0.02) were significantly associated with FFR values. An integrated assessment of AS (≥ or < 70%), MLA (≥ or < 2.5 mm 2 ) and presence or absence of thrombus and plaque ulceration was found to have the potential to accurately (sensitivity 91%, specificity 93%) predict FFR results. Conclusion In patients with ICL, a combination of different OCT parameters may help predict FFR results. These findings suggest that only a comprehensive assessment of lesion features by OCT can allow an accurate prediction of lesion severity assessed by FFR. [ABSTRACT FROM AUTHOR]