BACKGROUND/AIM: The effect of β-adrenergic blockers on everolimus-eluting stent (EES) implantation is unknown. We aimed to investigate how β-blockers affect the outcomes of EES by using the Tokyo-MD PCI registry data and analyse real-world data in this drug-eluting stent era in Japan. PATIENTS AND METHODS: We selected 1,899 patients who underwent EES implantation. We compared patients with β-blocker administration versus those without, at follow-up regarding the incidence rate of ischemia-driven target lesion revascularization (ID-TLR), all-cause death, cardiac death, acute myocardial infarction (AMI), and stent thrombosis (ST). RESULTS: Patients in the β-blocker group had higher coronary risks than those in the non-β-blocker group. Although no significant difference was observed in the five-year incidence of all-cause death, cardiac death, AMI, and ST between the two groups, the incidence of ID-TLR was significantly lower in the β-blocker group (4.5% vs. 6.6%; p=0.04). β-Blocker administration (hazard ratio=0.61; p=0.016) was negatively associated with ID-TLR via multivariate analysis. CONCLUSION: β-Blocker administration reduced ID-TLR after percutaneous coronary intervention using an EES despite the greater comorbid risks and more severe disease lesions.