<p>In-stent protrusion is sometimes observed after the stent implantation to the culprit lesion of ST-segment elevation myocardial infarction (STEMI). However, it remains unclear whether additional interventions are necessary for non-obstructive in-stent protrusions. The purpose of this retrospective study was to compare clinical outcomes of patients with STEMI between with and without angiographically visible in-stent protrusions, and to evaluate the association between angiographically visible in-stent protrusions and long-term clinical outcomes in patients with STEMI. We included 639 patients with STEMI who underwent stent implantation and divided them into the protrusion group (<i>n</i> = 59) and the clear stent group (<i>n</i> = 580). In-stent protrusion was defined as an angiographically visible in-stent contrast filling defect at final angiography. The primary endpoint was major adverse cardiovascular events (MACE), which were defined as the composite of all cause death, non-fatal myocardial infarction, and ischemia-driven target vessel revascularization. During the median follow-up duration of 620 (213–1379) days, MACE were more frequently observed in the protrusion group than in the clear stent group (<i>p</i> = 0.002). The multivariate Cox hazard analysis revealed that in-stent protrusion was significantly associated with MACE after controlling for multiple confounding factors (HR 2.373, 95% CI 1.311–4.294, <i>p</i> = 0.004). In conclusion, angiographically visible in-stent contrast filling defect at final angiography is a marker for worse clinical outcomes in primary PCI. When interventional cardiologists recognize visible irregular protrusion after stent implantation for STEMI, additional intervention or careful clinical follow up may be needed.</p> Graphical abstract <p></p>