Objective: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a useful inflammatory marker of cardiovascular risk, yet there are few reports on the prognostic significance of Lp-PLA2 as a risk factor for acute coronary syndrome (ACS). It is necessary to evaluate the association of Lp-PLA2 with major adverse cardiac events (MACE) in patients with ACS and assess its incremental value for risk discrimination over established risk factors and biomarkers. Methods: One hundred fifty-two patients with ACS and 142 patients without coronary artery disease (CAD) from Shanghai Xuhui District, PRC (aged < 80 years) were enrolled from February 2007 to March 2008 and were followed for a median of 6 months (range, 4–10 months). Plasma Lp-PLA2 activity was measured at baseline with liquid chromatography tandem mass spectrometry. Its clinical significance was evaluated with existing risk indicators. Results: Lp-PLA2 activity was higher in patients with ACS than in patients without CAD (22.36 ± 1.23 mg/mL vs 19.74 ± 3.85 mg/mL; P = 0.027). During the follow-up period, 5 cases of cardiovascular death, 8 cases of nonfatal myocardial infarction, and 11 cases of target vessel revascularization occurred. Elevated Lp-PLA2 was associated with an increased risk of MACE (hazard ratio, 1.52; 95% confidence interval, 1.09–2.37; P = 0.033). The Lp-PLA2 activity level in incidental cases was higher than in nonincidental cases (P = 0.04). Conclusion: In this community-based cohort of patients with ACS, Lp-PLA2 was strongly and independently associated with major adverse cardiac events and contributed incrementally to risk discrimination.