BACKGROUND Procedural and Clinical Outcomes still remain unfavorable for patients with long coronary lesions who undergo stent-based coronary interventions. Therefore, we compared the relative efficacy and safety of resolute zotarolimus-eluting stents (R-ZES) and sirolimus-eluting stents (SES) for patients with de novo long coronary lesions. METHODS and RESULTS This randomized, multicenter, prospective trial, called the LONG-DES IV trial, compared long R-ZES and SES in 500 patients with long (���25 mm) native coronary lesions. The primary end point of the trial was in-segment late luminal loss at 9-month angiographic follow-up. The baseline characteristics were not different between the R-ZES and SES groups, including lesion lengths (32.4짹13.5 mm vs. 31.0짹13.5 mm, P=0.27). At 9-months angiographic follow-up, the R-ZES was noninferior to the SES with respect to in-segment late luminal loss, the primary study end-point (0.14짹0.38 mm vs. 0.12짹0.43 mm, P for noninferiority=0.03, P for superiority=0.68). In addition, in-stent late luminal loss (0.26짹0.36 mm vs. 0.24짹0.42 mm, P=0.78) and the rates of in-segment (5.2% vs. 7.2%, P=0.44) and in-stent (4.0% vs. 6.0%, P=0.41) binary restenosis were not significantly different between the two groups. There were no significant between-group differences in the rate of adverse clinical events (death, myocardial infarction, stent thrombosis, target-lesion revascularization, and composite outcomes). CONCLUSIONS For patients with de novo long coronary artery disease, R-ZES implantation showed noninferior angiographic outcomes as compared with SES implantation.