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Mac-2 binding protein (M2BP) is an inflammatory glycoprotein associated with carotid atherosclerosis and all-cause mortality in patients with suspected coronary artery diseases. We aimed to explore the potential association of plasma M2BP levels with unstable plaque morphology and cardiovascular outcomes in patients with acute coronary syndrome (ACS).We compared plasma M2BP levels among three groups: 216 patients with ACS, 82 patients with stable angina pectoris, and 50 controls. Angiographic analyses of complex lesions were carried out in patients with ACS and they were followed up prospectively for 12 months for the occurrence of major adverse cardiovascular outcomes (MACEs).Patients with ACS showed significantly higher plasma levels of M2BP than patients with stable angina pectoris (P<0.001) and controls (P<0.001). M2BP levels correlated positively with the presence (P<0.001) and extent (P=0.005) of complex lesions. During follow-up, 45 (20.8%) cases of MACEs occurred. Survival analysis indicated that high M2BP levels were associated with a poor prognosis (log-rank P=0.008). After Cox multivariate adjustment, plasma M2BP levels remained an independent predictor of MACEs either as a continuous variable (hazard ratio: 1.178, 95% confidence interval: 1.093–1.270, P<0.001) or as a categorical variable (hazard ratio: 2.783, 95% confidence interval: 1.433–5.404, P=0.002).Plasma M2BP levels might be predictive of unstable plaque and were associated independently with poor cardiovascular outcomes in patients with ACS.