Objective To compare and observe the effects of drug-coated balloon (DCB) and drug-eluting stent (DES) in the treatment of de-novo diffuse long coronary lesions. Methods Totally 202 patients with de-novo diffuse long coronary lesions who underwent PCI were divided into the DCB group (68 patients with 72 lesions) and DES group (134 patients with 142 lesions) according to interventional strategy. Patients in the DCB group were treated with DCB only and patients in the DES group were treated with DES only. The differences between the two groups in terms of the immediate postoperative minimum lumen diameter (MLD), stenosis degree and lumen gain were observed. Coronary angiography fol⁃ low-up was performed within 6 to 12 months after PCI. We observed MLD, stenosis degree, late lumen loss, and net lu⁃ men gain at follow-up. The complications of the two groups at 12 months after PCI were also observed, including target le⁃ sion restenosis, target lesion revascularization (TLR), nonfatal myocardial infarction, and all-cause death. Results The immediate postoperative MLD and lumen gain in the DCB group were lower than those in the DES group (all P< 0. 05), and the immediate postoperative stenosis degree was higher in the DCB group (P<0. 05). The late lumen loss at follow-up in the DCB group was lower than in the DES group (P<0. 05). No significant differences were found in the rates of target lesion restenosis, TLR, nonfatal myocardial infarction, and all-cause death between two groups (all P>0. 05). Conclusion The immediate postoperative efficacy of DES was better than that of DCB in the treatment of de-novo diffuse long coronary lesions, but the late lumen loss of DCB was less. [ABSTRACT FROM AUTHOR]