Background: Minimal data exists regarding the safety and efficacy of drug-eluting stent (DES) in the treatment of intermediate coronary stenotic lesions. Therefore, we sought to compare the clinical, angiographic, and intravascular ultrasound (IVUS) findings between sirolimus-eluting stent (SES) and zotarolimus-eluting stent (ZES) for the intermediate stenotic lesions. Methods: Safety and efficacy of Endeavor stent (SAFE) trial is a multicenter, prospective, randomized trial to compare the outcomes between SES and ZES for the treatment of intermediate stenotic lesions, defined as 50-70% of angiographic diameter stenosis. We performed 9-month IVUS follow-up and followed the patients for 2 years. The primary end point was the amount of neointimal growth on 9-month IVUS follow-up. Results: A total of 204 patients were assigned into ZES (n=149) and SES (n=55), with 3:1 randomization. There was no significant difference in the baseline clinical and angiographic characteristics between ZES and SES. At 9-month follow-up, ZES group showed a significantly greater neointimal volume index and % neointimal volume obstruction, than SES (See table). However, the incidence of late-acquired malapposition was significantly lower in ZES (0.9%) than SES (30.8%, p<0.001). The rate of angiographic restenosis was similar between the groups. There were no significant differences in the 2 year major adverse cardiac events (MACE) and their individual components between ZES and SES. Conclusions: This study demonstrated that DES for the treatment of intermediate lesions was feasible and effective. In spite of a greater neointimal growth of ZES, ZES showed a lower incidence of late-acquired malapposition and the similar long-term clinical outcomes, not increasing the rates of restenosis or revascularization, compared with SES.