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Background Polarization-sensitive (PS-) optical frequency domain imaging (OFDI) measures polarization properties of tissue together with conventional cross-sectional OFDI images of subsurface microstructure. PS-OFDI offers refined insight into plaque morphology and composition, which are implicated in the pathogenesis of acute coronary syndromes (ACS). Purpose This first-in-human pilot study of intravascular polarimetry aimed to investigate birefringence and depolarization features of coronary plaques in patients and to examine the relationship of these features with established structural characteristics available to conventional OFDI and with clinical presentation. Methods 30 patients undergoing PS-OFDI (acute coronary syndrome; ACS, n=12 and stable angina pectoris; SAP, n=18) participated in this study. 342 cross-sectional images evenly distributed along all imaged coronary arteries were classified into one of seven plaque categories according to conventional OFDI. Polarization features averaged over the entire intimal area of each cross-section were compared between plaque types and with structural parameters. Further, we assessed the polarization properties in the fibrous caps of ACS and SAP culprit lesions and compared them with structural features using a generalized linear model. Results The median birefringence and depolarization showed statistically significant differences among plaque types (both p Intravascular polarimetry Conclusions Intravascular polarimetry provides quantitative metrics that help to characterize coronary arterial tissues and may offer refined insight into coronary arterial atherosclerotic lesions in patients (Figure). Quantitative assessment of plaque polarization properties by intravascular polarimetry may open new avenues for studying plaque progression and detecting high-risk patients. Acknowledgement/Funding The JSPS Overseas Research Fellowship, the Uehara Memorial Foundation, and the Japan Heart Foundation and Bayer Yakuhin