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Background: The hybrid strategy of drug-eluting stent (DES) and drug-coated balloon (DCB) has been increasingly accepted for the treatment of de novo coronary artery disease. However, data regarding the clinical outcome of this practice in a Southeast Asian population are limited., Aims: We aimed to investigate the safety and clinical outcome of this hybrid strategy (DES and DCB) in the treatment of de novo coronary artery disease. The primary endpoint was target lesion failure (TLF) in the DES/DCB-treated segment at 12 months. TLF is defined as the composite of cardiac death, target vessel myocardial infarction (TVMI) and ischaemia-driven target lesion revascularisation (ID-TLR) in the DES- and/or DCB-treated segment., Methods: A total of 401 patients with 458 lesions were treated with the hybrid strategy at the National Heart Institute (IJN), Kuala Lumpur, Malaysia, from 1 July 2021 to 30 June 2022, were retrospectively enrolled in the study. A total of 38 patients (9.5%) were lost to subsequent follow-up, and the remaining 363 patients (90.5%) were included in the outcome analysis. Clinical outcomes at 1 year were analysed., Results: In all, 219 lesions (47.8%) involved the left anterior descending artery, 146 lesions (31.9%) involved the right coronary artery, and 57 lesions (12.4%) involved the left circumflex artery. In all, 87 lesions (19%) were bifurcation lesions. A total of 8 patients (2.2%) had TLF, of whom 3 patients (0.83%) had TVMI, 3 patients (0.83%) had ID-TLR, and 2 patients (0.6%) experienced cardiac death. Four patients died of a non-cardiac cause at 1-year follow-up., Conclusions: A hybrid strategy of DES and DCB for the treatment of de novo coronary artery lesions appears to be feasible and clinically safe according to the 1-year outcomes., Competing Interests: The authors have no conflicts of interest to declare.