BACKGROUND AND OBJECTIVES: The clinical implication of high-degree (second- and third-degree) atrioventricular block (HAVB) complicating ST-segment elevation myocardial infarction (STEMI) is ripe for investigation in this era of primary percutaneous coronary intervention (PCI). We sought to address the incidence, predictors and prognosis of HAVB according to the location of infarct in STEMI patients treated with primary PCI. SUBJECTS AND METHODS: A total of 16536 STEMI patients (anterior infarction: n=9354, inferior infarction: n=7692) treated with primary PCI were enrolled from a multicenter registry. We compared in-hospital mortality between patients with HAVB and those without HAVB with anterior or inferior infarction, separately. Multivariate analyses were performed to unearth predictors of HAVB and to identify whether HAVB is independently associated with in-hospital mortality. RESULTS: STEMI patients with HAVB showed higher in-hospital mortality than those without HAVB in both anterior (hazard ratio [HR]=9.821, 95% confidence interval [CI]: 4.946-19.503, p<0.001) and inferior infarction (HR=2.819, 95% CI: 2.076-3.827, p<0.001). In multivariate analyses, HAVB was associated with increased in-hospital mortality in anterior myocardial infarction (HR=19.264, 95% CI: 5.804-63.936, p<0.001). However, HAVB in inferior infarction was not an independent predictor of increased in-hospital mortality (HR=1.014, 95% CI: 0.547-1.985, p=0.901). CONCLUSION: In this era of primary PCI, the prognostic impact of HAVB is different according to the location of infarction. Because of recent improvements in reperfusion strategy, the negative prognostic impact of HAVB in inferior STEMI is no longer prominent.