To investigate the clinical significance of bright spots in coronary plaque detected by optical coherence tomography (OCT) in patients with coronary artery disease. We identified 112 patients [acute coronary syndromes (ACS): n = 50, stable angina pectoris (SAP): n = 62] who underwent OCT imaging of the culprit lesion. A novel OCT algorithm was applied to detect bright spots representing the juxtaposition of a variety of plaque components including macrophages. The density of bright spots within the most superficial 250 μm of the vessel wall was measured at the site of culprit lesion. Bright spot density in the culprit lesion was significantly higher in patients presenting with ACS compared to those presenting with SAP (0.51 ± 0.43 % vs. 0.37 ± 0.26 %, P = 0.04), particularly in the subgroup with ruptured culprit plaque (0.59 ± 0.52 %). Thin-cap fibroatheroma (TCFA) was associated with a trend towards a higher density of bright spots compared to non-TCFA plaques (0.57 ± 0.50 % vs. 0.41 ± 0.31 %, P = 0.08). Similar results were also obtained within 1000 μm depth. Positive linear correlation was demonstrated between bright spot density and hsCRP level (r = 0.45, P = 0.002). Using a novel algorithm, we demonstrated a significantly higher density of bright spots in the culprit lesions of patients presenting with ACS, particularly in case of plaque rupture, compared to those presenting with SAP. The density of bright spots also correlates with inflammatory status. These results suggest that the quantitative assessment of bright spot density may be useful in evaluating plaque vulnerability.