Aim To compare the long-term effects of drug-coated balloon angioplasty and drug-eluting stent implantation for left main bifurcation(LMB)-in-stent restenosis(ISR). Methods 48 patients with LMB-ISR, who underwent percutaneous coronary intervention (PCI) between October 2014 and October 2018, were retrospectively reviewed for the present study (repeat drug eluting stent (DES) implantation (n＝24), DCB angioplasty (n＝24)). Qualitative comparative analysis (QCA) was performed before and after PCI. Thirty-nine patients (81.3%) were followed up for 18 months to perform coronary angiography(CAG) and QCA, and long-term follow-up was conducted for clinical endpoint events. Results Analysis of the baseline characteristics showed that the patients in the DCB group had a similar incidence of non-ST segment elevation myocardial infarction/ST segment elevation myocardial infarction at the index PCI (8.3% vs 25.0%, P＝0.25), higher low-density lipoprotein cholesterol level ((92.9±35.1) mg/dL vs (78.0±30.7) mg/dL, P＝0.07), and more “stent- in-stent” lesions (25.0% vs 4.2%, P＝0.05) than those in the DES group but not statistically significant. After 18 months follow up ,QCA showed there was no significant difference between the DCB group and the DES group in the late lumen loss ((1.06±1.10) mm vs (0.84±1.15) mm, P＝0.62), and no significant difference in the minimum lumen diameter of target lesions ((1.68±0.96) mm vs (2.06±1.21) mm, P＝0.37). The cumulative incidence rates of major adverse cardiovascular events (MACE) were similar between both groups (median follow-up duration was 868 days; MACE rate was 25.0% in the DCB group and 29.2% in the DES group, P＝0.75). Conclusion DES and DCB showed comparable long-term clinical results in patients with LMB-ISR lesions.