Background: The precursor of plaque rupture is known as thin cap fibroatheroma (TCFA). In the present study, the feasibility and accuracy of optical coherence tomography (OCT) for detecting the frequency and spatial distribution of TCFA was investigated ex vivo, and a 3-vessel OCT analysis was conducted to assess the feasibility of this modality in vivo. Methods and Results: In the ex vivo study, 108 coronary arterial segments from 38 human cadavers were examined by OCT, intravascular ultrasound (IVUS) and histology. The 3-vessel IVUS and OCT examinations were performed in 11 patients with acute coronary syndrome. By histological examination, 30 of 77 fibroatheromas were diagnosed as TCFAs, which showed a clear pattern of clustering in the proximal part of each coronary vessel. OCT accurately detected TCFA (sensitivity 90%, specificity 79%). The in vivo OCT study showed that 64% patients with acute coronary syndrome had 1 or more TCFAs. Conclusions: TCFAs, clustering in the proximal segments of the 3 major epicardial coronary arteries, are a common finding in unselected autopsy subjects. OCT is a feasible and accurate modality for detecting TCFA both ex vivo and in vivo. (Circ J 2009; 73: 1086-1091)