Objective: Although monocytes appear to be actively involved in the onset of acute coronary syndrome (ACS), they are heterogenous in human peripheral blood. How up-regulation of monocyte subsets leads to coronary plaque rupture followed by thrombus formation remains unclear. Recent studies have shown that P-selectin glycoprotein ligand-1 (PSGL-1) is involved in monocyte activation in patients with thrombus formation. We therefore investigated the relationship between the expression of PSGL-1 on monocyte subsets and thrombus formation using frequency-domain optical coherence tomography (FD-OCT) in patients with ACS. Methods: We enrolled a total of 100 individuals in this study: patients with acute myocardial infarction (AMI, n = 25), unstable angina pectoris (UAP, n = 20), or stable angina pectoris (n 35) who underwent coronary angiography, and control subjects (n = 20). Three monocyte subsets (CD14(++)CD16(-) , CD14(++)CD16(+), and CD14(+)CD16(+)) and the expression of PSGL-1 were measured by flow cytometry. In patients with AMI and UAP, FD-OCT was performed before percutaneous coronary intervention. Results: Circulating peripheral CD14(++)CD16(+) monocytes expressed PSGL-1 more frequently than CD14(++)CD16(+) and CD14(++)CD16(+) monocytes in patients with ACS. The expression of PSGL-1 on circulating peripheral CD14(++)CD16(+) monocytes was significantly elevated in patients with AMI compared with the other 3 groups. Moreover, the expression levels of PSGL-1 on CD14(++)CD16(+) monocytes were significantly higher in patients with plaque rupture or intracoronary thrombus assessed by FD-OCT. Conclusion: Up-regulation of PSGL-1 on CD14(++)CD16(+) monocytes may be a crucial role in plaque rupture and thrombus formation. (C) 2014 Elsevier Ireland Ltd. All rights reserved.