OBJECTIVES: We attempted to characterize the anatomy, function, clinical consequences, and treatment of right-sided anomalous coronary artery origin from the opposite side (R-ACAOS). BACKGROUND: Anomalous aortic origin of a coronary artery is a source of great uncertainty in cardiology. A recent study by our group found that ACAOS had a high prevalence (0.48%) in a general population of adolescents. METHODS: Sixty-seven consecutive patients were diagnosed with R-ACAOS according to a new definition: ectopic right coronary artery (RCA) with an intramural proximal course. We used intravascular ultrasonograms of the RCA to quantify congenital stenosis (in patients with potentially serious clinical presentations), and we correlated these measurements with clinical manifestations. RESULTS: All patients had some proximal intramural stenosis (mean 50%, range 16-83% of the cross-sectional area). Forty-two patients (62%) underwent stent-percutaneous coronary intervention (PCI) of R-ACAOS because of significant symptoms, positive stress tests, and/or significant stenosis. Stent-PCI was successful in all cases and correlated with improved symptoms at >1-year follow-up in 30 patients (71%) who were available for clinical follow-up. No ACAOS-related deaths occurred. The instent restenosis rate was 4/30 (13%) at a mean follow-up time of 5.0 years. CONCLUSIONS: This preliminary, but large and unprecedented observational study shows that cases angiographically identified as R-ACAOS universally feature an intramural aortic course but only occasionally severe stenosis on resting IVUS imaging. Our data suggest that stent-PCI with IVUS monitoring ameliorates patients' presenting symptoms.