The present study aims to clarify the long-term clinical importance of interleukin (IL)-6 in predicting major adverse cardiac events (MACE) for an entire cohort of patients with coronary artery disease after implantation of a drug-eluting stent (DES), and its interplay with periprocedural myocardial infarction (PMI). Background: The correlation of proinflammatory biomarkers with occurrence of clinical events, including PMI and mortality, is controversial. Methods: IL-6 was measured in 1,991 patients at admission. The participants were then assigned to two groups: IL-6 level $9 pg/mL and IL-6 level ,9 pg/mL. The primary endpoint was the occurrence of cardiac death or myocardial infarction (MI) at year 3 after indexed percutaneous coronary intervention (PCI) procedure. Results: The in-hospital rate of the primary endpoint in the IL-6 level $9 pg/mL group was 9.1%, statistically significantly different to 6.3% in the IL-6 ,9 pg/mL group (P=0.026), mainly driven by the increased rate of MI (9.1% vs 6.1%, P=0.025). Those differences in MI/death and MI was sustained through to the 3-year follow-up (10.9% vs 7.6%, P=0.017 and 10.1% vs 7.5%, P=0.049). At the 3-year follow-up after the assigned procedure, more frequent MI was also the main reason for increased composite MACE between the IL-6 $9 pg/mL and IL-6 ,9 pg/mL groups (20.7% vs 15.8%, P=0.007). In the IL-6 $9 pg/mL group, PMI was strongly correlated with mortality at 1-year through to the 3-year (hazard ratio: 2.96, 95% confidence interval: 1.35-6.49, P=0.005) follow-up after PCI procedure. Conclusion: Elevated preprocedural serum IL-6 level was correlated with death, MI, and MACE after implantation of the DES. PMI enhances the predictive value of IL-6 for post-DES events.