Background Available drug-eluting stents (DES) have achieved great success in reducing restenosis rates. Recently,investigators have demonstrated that the durable polymer carrier plays a significant role in DES-related hypersensitive reaction and delays vessel healing. TIVOLI stent is a novel sirolimus-eluting coronary stent with biodegradable coating containing sirolimus and polylactic-co-glycolic acid (PLGA) polymer. The present study sought to evaluate the effectiveness and safety of the TIVOLI biodegradable-polymer-based sirolimus-eluting stent in treating patients with coronary artery disease.Methods A prospective, multicenter clinical trial comparing TIVOLI biodegradable coated sirolimus-eluting stent with ENDEAVOR zotarolimus-eluting stent was conducted in 324 patients (TIVOLI group: 168 patients; ENDEAVOR group:156 patients) at 12 centers in China to demonstrate the non-inferiority of in-stent late loss with TIVOLI stent compared to ENDEAVOR stent in subjects with a maximum of two de novo native coronary artery lesions (lesion length ≤40 mm,reference vessel diameter 2.25-4.00 mm). The primary end point was angiographic in-stent late loss at 8-month. The secondary end points were clinical outcomes at 2 years,including major adverse cardiac events (cardiac death,myocardial infarction, or target-lesion revascularization) and stent thrombosis.Results Angiographic late lumen loss at 8 months in the TIVOLI group was superior to the ENDEAVOR group (in-stent (0.25±0.33) mm vs. (0.57±0.55) mm, diff (95% CI)-0.23 (-0.32, -0.14), P ＜0.0001; in-segment (0.25±-0.33) mm vs. (0.42±-0.55) mm, diff (95% CI) -0.13 (-0.23, -0.02),P=0.0083). The rate of in-stent binary restenosis at 8 months was reduced from 8.6% in the ENDEAVOR group to 2.9% in the TIVOLI group (P=0.0229). Compared to ENDEAVOR stent, TIVOLI stent resulted in a significant reduction in target-lesion revascularization (4.2% vs. 9.6%, P=0.0495) at 2 years. The two-year major adverse cardiac events (MACE) rate was lower for the TIVOLI group, but not significantly different (6.6% vs. 10.9%, P=0.1630).Conclusions TIVOLI was superior to ENDEAVOR stent with respect to late lumen loss at 8 months, and it yielded both lower rates of angiographic binary restenosis at 8 months and target lesion revascularization (TLR) at 2 years.The MACE rate at 2 years was comparable in both groups.