Background First generation drug-eluting stents (DES) were associated with a high incidence of late stent thrombosis (ST), mainly due to delayed healing and re-endothelization by the durable polymer coating. This study sought to assess the safety and efficacy of the Nano polymer-free sirolimus-eluting stent (SES) in the treatment of patients with de novo coronary artery lesions. Methods The Nano trial is the first randomized trial designed to compare the safety and efficacy of the Nano polymer-free SES and Partner durable-polymer SES (Lepu Medical Technology, Beijing, China) in the treatment of patients with de novo native coronary lesions. The primary endpoint was in-stent late lumen loss (LLL) at 9-month follow-up. The secondary endpoint was major adverse cardiac events (MACE), a composite of cardiac death, myocardial infarction or target lesion revascularization. Results A total of 291 patients (Nano group: n=143, Partner group: n=148) were enrolled in this trial from 19 Chinese centers. The Nano polymer-free SES was non-inferior to the Partner durable-polymer DES at the primary endpoint of 9 months (P <0.001). The 9-month in-segment LLL of the polymer-free Nano SES was comparable to the Partner SES (0.34 +/- 0.42) mm vs. (0.30 +/- 0.48) mm, P=0.21). The incidence of MACE in the Nano group were 7.6% compared to the Partner group of 5.9% (P=0.75) at 2 years follow-up. The frequency of cardiac death and stent thrombosis was low for both Nano and Partner SES (0.8% vs. 0.7%, 0.8% vs. 1.5%, both P=1.00). Conclusions In this multicenter randomized Nano trial, the Nano polymer-free SES showed similar safety and efficacy compared with the Partner SES in the treatment of patients with de novo coronary artery lesions. Trials in patients with complex lesions and longer term follow-up are necessary to confirm the clinical performance of this novel Nano polymer-free SES.