Background: We aimed to assess the relationships of pentraxin-3 (PTX3) with coronary plaque components and myocardial perfusion after percutaneous coronary intervention (PCI) in order to clarify the mechanisms underlying the prognostic function of PTX3 in ST-elevation acute myocardial infarction (STEMI) patients. Methods and Results: We enrolled 75 STEMI patients who underwent pre-PCI virtual histology (VH)-intravascular ultrasound. Relationships of the systemic pre-PCI PTX3 level with coronary plaque components and post-PCI myocardial blush grade (MBG) were evaluated. Lesions with elevated pre-PCI PTX3 (median ≥3.79ng/ml) had higher frequencies of VH-derived thin-cap fibroatheroma (65.8% vs. 24.3%, P<0.0001), plaque rupture (63.2% vs. 24.3%, P=0.001), and post-PCI MBG (0–1) (65.8% vs. 40.5%, P=0.03) than those with PTX3 <3.79ng/ml. In multivariate analysis, pre-PCI PTX3 level was independently related to post-PCI MBG (0–1) (odds ratio, 11.385; 95% confidence interval (CI), 1.346–96.289; P=0.026). At 9-month follow-up, cardiac event-free survival was poorer for patients with post-PCI MBG (0–1) (log-rank test χ²=8.6; P=0.003). Cox proportional-hazards analysis showed post-PCI MBG (0–1) (hazard ratio, 4.109; 95% CI, 1.372–12.309; P=0.012) and Killip class >2 on admission (hazard ratio, 5.356; 95% CI, 1.409–20.359; P=0.014) as independent predictors of adverse cardiac events during follow-up. Conclusions: Systemic pre-PCI PTX3 was associated with high-risk plaque components and impaired post-PCI myocardial perfusion. Thus, PTX3 may be a reliable predictor of outcome in STEMI patients.  (Circ J 2014; 78: 159–169)