OBJECTIVE Lipoprotein-associated phospholipase A₂ (Lp-PLA₂) is an inflammatory enzyme expressed in atherosclerotic plaques. We investigated the association of circulating Lp-PLA₂ with characteristics of vulnerable coronary atherosclerotic plaques. METHODS We recruited 113 patients with either unstable angina (UA, n=59) and stable angina (SA, n=54) by coronary angiography. Thirty-six healthy subjects served as controls. Intravascular ultrasound (IVUS) was used to evaluate the characteristics of coronary atherosclerotic plaque, and serum Lp-PLA₂ concentration was measured as well. RESULTS Lp-PLA₂ concentration was significantly higher in both UA and SA patients [(396±36) μg/L and (321±39) μg/L, respectively] compared with the controls [(127 ± 49) μg/L, p<0.01], and higher in UA than SA group. IVUS findings showed that remodeling index (RI) (0.91 ± 0.15 vs. 0.85 ± 0.11, p=0.005) and eccentricity index (EI) (0.73 ± 0.16 vs. 0.65 ± 0.22, p=0.039) were larger in UA than in SA group, and fibrous caps were thicker in SA than UA group [(0.91 ± 0.23) mm vs. (0.63 ± 0.21) mm, p=0.032]. Moreover, Lp-PLA₂ correlated positively with EI (r=0.439, p<0.01) and RI (r=0.592, p<0.05) in UA group. There was an inverse relationship between Lp-PLA₂ and fibrous cap thickness in both UA (r=-0.587, p<0.001) and SA (r=-0.318, p<0.05) groups. The independent risk factors in UA group were Lp-PLA₂ (OR=1.055, 95% CI: 1.03-1.08, p=0.013), LDL-cholesterol (OR=0.032, 95% CI: 0.00-0.05, p=0.041) and fibrous cap thickness (OR=0.008, 95% CI: 0.00-0.45, p=0.019). Lp-PLA₂ was strongly associated with both EI and fibrous cap thickness in both groups. CONCLUSIONS Serum level of Lp-PLA₂ is associated with both eccentricity index and fibrous cap thickness in both UA and SA groups. Elevated levels of circulating Lp-PLA₂ might to be a strong risk factor and more serious for unstable angina than stable angina.