To investigate the clinical utility of culprit plaque characteristics and inflammatory markers for the prediction of future cardiovascular events in patients with ST-segment elevation myocardial infarction (STEMI) with successful drug-eluting stent (DES) implantation. We evaluated 172 STEMI patients with successful primary percutaneous coronary intervention (PCI) with DES using pre-PCI high-sensitivity C-reactive protein (hs-CRP), neutrophil-to-lymphocyte ratio (NLR) and pre-PCI intravascular ultrasound virtual histology (IVUS-VH) of culprit lesions. The incidence of major adverse cardiovascular events (MACE) including all-cause mortality, non-fatal MI, stroke and late revascularization were recorded during hospitalization and follow-up. During follow-up (median 41 months), the incidence of MACE did not significantly differ among patients with or without all 3 high-risk plaque features on IVUS-VH (15.1 vs. 16.2%; p = 0.39). In contrast, patients with elevated hs-CRP and NLR levels were at significant risk for MACE [32.7 vs. 5.8%; hazard ratio (HR) 7.85; p < 0.001 and 43.9 vs. 6.9%; HR 8.44; p < 0.001, respectively]. High-risk plaque features had no incremental usefulness to predict future MACE. However, the incorporation of hs-CRP and NLR into a model with conventional clinical and procedural risk factors significantly improved the C-statistic for the prediction of MACE (0.76–0.89; p = 0.04). High-risk plaque features identified by IVUS-VH in culprit lesions were not associated with future MACE in patients with STEMI receiving DES. However, elevated hs-CRP and NLR levels were significantly associated with poorer outcomes and had incremental predictive values over conventional risk factors.