Introduction: Increased levels of the inflammatory cytokine interleukin 6 (IL-6) after percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) are associated with larger infarct size and decreased cardiac function. Early treatment with the IL-6 receptor inhibitor tocilizumab in STEMI patients resulted in less myocardial damage, especially in patients treated >3 hours after symptom onset. However, the specific window of opportunity for IL-6 inhibition in STEMI patients remains to be investigated. Therefore, we studied IL-6 levels in STEMI patients varying in ischemic time (i.e. time from symptom onset to PCI), and its association with infarct size. Methods: In 369 STEMI patients IL-6 levels were measured at 24 hours post-PCI. Patients were categorized according to ischemic time (<2 hours, 2-3 hours, 3-4 hours, 4-5 hours, >5 hours). At 4 months, infarct size was assessed by magnetic resonance imaging. IL-6 levels were log transformed for statistical analysis. Results: IL-6 levels at 24 hours post-PCI increased from 9.2 ng/ml (IQR 5.2-16.7 ng/ml) in patients with symptom onset <2 hours to 13.2 ng/ml (IQR 9.0-20.2 ng/ml) in patients with symptom onset between 4-5 hours (P trend =0.036), stabilizing in patients with symptom onset >5 hours ( Figure 1A ). Higher IL-6 levels at 24 hours post-PCI were associated with larger infarct size in patients with symptom onset <4 hours (<2 hours: β 1.9, 95% CI 0.6-3.1, P=0.004; 2-3 hours: β 1.9, 95% CI 0.3-3.4, P=0.019; 3-4 hours: β 3.0, 95% CI 1.6-4.5, P<0.001) ( Figure 1B ). Conclusions: IL-6 levels at 24 hours post-PCI are related to ischemic time. Moreover, higher IL-6 levels are associated with larger infarct size in patients with ischemic time shorter than 4 hours, suggesting a time dependent role of IL-6. This suggests that the window of opportunity for IL-6 inhibition in STEMI patients is within 4 hours of symptom onset. Randomized controlled trials are necessary to further establish this relationship.