We aimed to investigate the association between local interleukin-6 (IL-6) levels at the infarct-related artery and the risk of slow flow/microvascular dysfunction after PCI in ST-elevation acute myocardial infarction (AMI) patients treated by successful primary PCI. 56 eligible ST-elevation AMI patients (34 male/22 female, mean age: 63.5 ± 10.3 years), undergoing successful primary PCI, were included in the current study. Blood samples were obtained from the extraction catheter placed distal to the lesion before PCI. Plasma IL-6 levels were determined by immunoassay method. Slow flow/microvascular dysfunction was observed in 21 patients (37.5%). Using multiple logistic regression analysis, local IL-6 levels (OR 1.592, CI 1.135-2.268; P = 0.007) were found to be a significant risk factor of slow flow/microvascular dysfunction together with diabetes mellitus (OR = 8.065, CI 1.244-52.632; P = 0.029) and thrombus score (OR = 12.500, CI 1.100-142.857; P = 0.042). Receiver operating characteristic (ROC) curve analysis revealed that local IL-6 (ROC area 0.824, OR 1.704, CI 1.274-2.281, P < 0.001; optimal threshold ≥11.3 pg/ml) had a predictive value of slow flow/microvascular dysfunction with sensitivity of 73% and specificity of 71%. Our study indicated that inflammatory response as presented by local IL-6 levels was associated with slow flow/microvascular dysfunction in patients with ST-elevation AMI after successful primary PCI.