ABSTRACT: OBJECTIVE:To examine the fractional flow reserve derived from computed tomographic angiography (CT-FFR) in patients with anomalous origin of the right coronary artery from the left coronary sinus (R-ACAOS) with an interarterial course, assess the relationship of CT-FFR with the anatomical features of interarterial R-ACAOS on coronary computed tomographic angiography (CCTA), and determine its clinical relevance. MATERIALS AND METHODS:Ninety-four patients with interarterial R-ACAOS undergoing CCTA were retrospectively included. Anatomic features (proximal vessel morphology [oval or slit-like], take-off angle, take-off level [below or above the pulmonary valve], take-off type, intramural course, % proximal narrowing area, length of narrowing, minimum luminal area [MLA] at systole and diastole, and vessel compression index) on CCTA associated with CT-FFR ? 0.80 were analyzed. Receiver operating characteristic analysis was performed to describe the diagnostic performance of CT-FFR ? 0.80 in detecting interarterial R-ACAOS. RESULTS:Significant differences were found in proximal vessel morphology, take-off level, intramural course, % proximal narrowing area, and MLA at diastole (all p < 0.05) between the normal and abnormal CT-FFR groups. Take-off level, intramural course, and slit-like ostium (all p < 0.05) predicted hemodynamic abnormality (CT-FFR ? 0.80) with accuracies of 0.69, 0.71, and 0.81, respectively. Patients with CT-FFR ? 0.80 had a higher prevalence of typical angina (29.4% vs. 7.8%, p = 0.025) and atypical angina (29.4% vs. 6.5%, p = 0.016). CONCLUSION:Take-off level, intramural course, and slit-like ostium were the main predictors of abnormal CT-FFR values. Importantly, patients with abnormal CT-FFR values showed a higher prevalence of typical angina and atypical angina, indicating that CT-FFR is a potential tool to gauge the clinical relevance in patients with interarterial R-ACAOS.