The aims of this study are to evaluate the efficacy of percutaneous coronary intervention (PCI) using full-metal jacket (FMJ) with second-generation drug-eluting stents (DES). A single-center, non-randomized, retrospective study was performed from May 2005 to February 2014 at Miyazaki Medical Association Hospital, Japan. PCI using FMJ with DES was performed to treat 240 very long lesions (> 60 mm) in 240 patients. Subjects were divided into a first-generation or second-generation DES group. The primary endpoint was the incidence of major adverse cardiac events (MACE) at 2 years. MACE included all-cause death, myocardial infarction (MI), cerebrovascular event, and target vessel revascularization. The secondary endpoint was binary restenosis (> 50% stenosis) assessed by angiography at 1 year of follow-up. Second-generation DES were implanted to treat 121 lesions, and the first-generation DES were implanted to treat 119 lesions. Since 35 patients were lost to follow-up, the final analysis included 102 patients with second-generation DES and 103 with first-generation DES. At the 2-year follow-up, the incidence of MACE was significantly less in the second-generation DES group (9.8% vs. 20.4%, p = 0.03). The incidence of binary restenosis at 1 year was also significantly lower in the second-generation DES group (6.7% vs 29.1%, p < 0.01). When PCI was performed using FMJ with DES to treat very long lesion, the angiographic and clinical outcomes were better with second-generation than first-generation DES.